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1.
Arch Toxicol ; 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39361050

RESUMEN

Thallium (Tl) is one of the most toxic heavy metals, associated with accidental poisoning and homicide. It causes acute and chronic systemic diseases, including gastrointestinal and cardiovascular diseases and kidney failure. However, few studies have investigated the mechanism by which Tl induces acute kidney injury (AKI). This study investigated the toxic effects of Tl on the histology and function of rat kidneys using biochemical and histopathological assays after intraperitoneal thallium sulfate administration (30 mg/kg). Five days post-administration, rats exhibited severely compromised kidney function. Low-vacuum scanning electron microscopy revealed excessive calcium (Ca) deposition in the outer medulla of Tl-loaded rats, particularly in the medullary thick ascending limb (mTAL) of the loop of Henle. Tl accumulated in the mTAL, accompanied by mitochondrial dysfunction in this segment. Tl-loaded rats showed reduced expression of kidney transporters and channels responsible for Ca2+ reabsorption in the mTAL. Pre-administration of the Na-K-Cl cotransporter 2 (NKCC2) inhibitor furosemide alleviated Tl accumulation and mitochondrial abnormalities in the mTAL. These findings suggest that Tl nephrotoxicity is associated with preferential Tl reabsorption in the mTAL via NKCC2, leading to mTAL mitochondrial dysfunction and disrupted Ca2+ reabsorption, culminating in mTAL-predominant Ca crystal deposition and AKI. These findings on the mechanism of Tl nephrotoxicity may contribute to the development of novel therapeutic approaches to counter Tl poisoning. Moreover, the observation of characteristic Ca crystal deposition in the outer medulla provides new insights into diagnostic challenges in Tl intoxication.

2.
Med Mol Morphol ; 56(3): 206-216, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37165248

RESUMEN

To improve the resolution of low-vacuum scanning electron microscopy (LVSEM), the epoxy resin block for the transmission electron microscopy (TEM) was observed directly with LVSEM. After observing ultrathin sections from renal biopsies of IgA nephropathy, membranous nephropathy, lupus nephritis, diabetic nephropathy (DM), thin basement membrane disease (TBMD), Alport's syndrome, Fabry's disease, and renal amyloidosis, the epoxy resin blocks of the same sites were observed by LVSEM and compared. The LVSEM image of the epoxy resin block corresponds to the negative of the TEM image, and when the gradation is reversed, the LVSEM image was comparable to the TEM image. At a low magnification of 100 ×, the entire specimen, including the glomerulus, was obtained. LVSEM at 5000 × magnification was sufficient to identify paramesangial deposits in IgA nephropathy and subepithelial electron-dense deposits (EDD) and spikes in membranous nephropathy. Glomerular basement membrane thickening in DM and thinning in TBMD could be sufficiently diagnosed with LVSEM at 6000 ×. Accumulation of ceramide in Fabry's disease was easily identified, but amyloid fibril could not be identified by LVSEM. LVSEM of renal biopsy epoxy resin blocks can replace TEM up to moderate magnification.


Asunto(s)
Enfermedad de Fabry , Glomerulonefritis por IGA , Humanos , Microscopía Electrónica de Rastreo , Resinas Epoxi , Vacio , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/patología , Biopsia
3.
Med Mol Morphol ; 55(2): 123-130, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35122146

RESUMEN

Purple urine bag syndrome (PUBS) is seen in the prolonged indwelling bladder catheters, and the mechanism of its onset was investigated using low vacuum scanning electron microscopy (LVSEM), which enables us to study the 3D structure of urinary sediments and urine bag walls. The urinary sediment and urine bags of 2 cases of PUBS were observed by LVSEM. The urine was brown turbid urine with a pH of 8.5, and magnesium phosphate stones and granules were observed in the urinary sediment together with Gram-positive and Gram-negative bacilli. Bacteria that moved by Brownian motion were observed with a dark-field microscope. LVSEM showed granular crystals around the bacilli, cocci, or mycelium that adhered to the walls of the bag. Granular crystals were dissolved in chloroform and presumed to be a mixture of the bacterial metabolites indigo blue and indirubin red. LVSEM also detected unusual tubular and honeycomb-like graphene in the urinary sediments, which were derived from the inner layer of the silicon elastomer-coated rubber catheter. LVSEM revealed purple crystals produced by bacteria or fungi attached to the urine bag that caused PUBS.


Asunto(s)
Infecciones Urinarias , Catéteres de Permanencia , Humanos , Microscopía Electrónica de Rastreo , Síndrome , Cateterismo Urinario , Infecciones Urinarias/microbiología , Vacio
4.
Int J Mol Sci ; 22(24)2021 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-34948207

RESUMEN

In minimal change nephrotic syndrome, podocyte vesicle transport is enhanced. Adenomatous polyposis coli (APC) anchors microtubules to cell membranes and plays an important role in vesicle transport. To clarify the role of APC in vesicle transport in podocytes, nephrotic syndrome was induced by puromycin amino nucleoside (PAN) injection in mice expressing APC1638T lacking the C-terminal of microtubule-binding site (APC1638T mouse); this was examined in renal tissue changes. The kidney size and glomerular area of APC1638T mice were reduced (p = 0.014); however, the number of podocytes was same between wild-type (WT) mice and APC1638T mice. The ultrastructure of podocyte foot process was normal by electron microscopy. When nephrotic syndrome was induced, the kidneys of WT+PAN mice became swollen with many hyaline casts, whereas these changes were inhibited in the kidneys of APC1638T+PAN mice. Electron microscopy showed foot process effacement in both groups; however, APC1638T+PAN mice had fewer vesicles in the basal area of podocytes than WT+PAN mice. Cytoplasmic dynein-1, a motor protein for vesicle transport, and α-tubulin were significantly reduced in APC1638T+PAN mice associated with suppressed urinary albumin excretion compared to WT+PAN mice. In conclusion, APC1638T mice showed reduced albuminuria associated with suppressed podocyte vesicle transport when minimal change nephrotic syndrome was induced.


Asunto(s)
Poliposis Adenomatosa del Colon/patología , Albuminuria/patología , Síndrome Nefrótico/patología , Podocitos/patología , Transcitosis/fisiología , Poliposis Adenomatosa del Colon/metabolismo , Albuminuria/metabolismo , Animales , Modelos Animales de Enfermedad , Glomérulos Renales/metabolismo , Glomérulos Renales/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Síndrome Nefrótico/inducido químicamente , Síndrome Nefrótico/metabolismo , Podocitos/metabolismo , Puromicina/farmacología , Puromicina Aminonucleósido/farmacología
5.
Med Mol Morphol ; 51(2): 89-95, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29318388

RESUMEN

Vacuolar H+-adenosine triphosphatase (ATPase) plays important roles in urinary acid excretion, vesicular acidification to activate enzymes, and the membrane recycling of transporters in the kidney. As acidosis stimulates renal gluconeogenesis, we investigated the effect of blockade of H+-ATPase on renal gluconeogenesis in diabetic rats. Diabetes mellitus was induced by a single injection of streptozotocin, and a group of DM rats was treated with bafilomycin B1 intraperitoneally for 8 days. In diabetic rats, the renal expression and activity of H+-ATPase were increased with elevated urinary ammonium excretion. The blockade of H+-ATPase by bafilomycin B1 reduced the renal H+-ATPase activity and urinary ammonium excretion in diabetic rats. Treatment with bafilomycin suppressed the enhancement of the renal gluconeogenesis enzymes phosphoenol pyruvate carboxykinase and glucose-6-phosphatase in diabetic rats and reduced the renal cytoplasmic glucose levels, whereas hepatic gluconeogenesis did not change significantly. After a 24-h starvation period, bafilomycin decreased the plasma glucose level to a normal level in diabetic rats. The suppression of renal gluconeogenesis by an H+-ATPase inhibitor may therefore be a new therapeutic target for the treatment of diabetes mellitus.


Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Macrólidos/farmacología , ATPasas de Translocación de Protón/antagonistas & inhibidores , Compuestos de Amonio/metabolismo , Animales , Citoplasma/metabolismo , Inhibidores Enzimáticos/farmacología , Gluconeogénesis/efectos de los fármacos , Glucosuria , Riñón/efectos de los fármacos , Riñón/metabolismo , ATPasas de Translocación de Protón/metabolismo , Ratas Sprague-Dawley , Transportador 2 de Sodio-Glucosa/metabolismo , Inanición
6.
Med Mol Morphol ; 50(2): 86-93, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28314927

RESUMEN

Albumin endocytosis is enhanced in the podocytes of minimal change nephrotic syndrome. We investigated that the endocytic vesicle transport in the podocyte using three-dimensional observation in a rat model of puromycin aminonucleoside (PAN)-induced nephrotic syndrome. At day 7, Evans Blue-labeled albumin was intravenously injected in PAN rats, and one kidney was fixed for a morphological analysis; the other was used for the isolation of glomeruli through sieving and protein analyses. Evans Blue-labeled albumin was found to accumulate in an increased number of vesicles in the podocytes of PAN rat. Continuous sections and its three-dimensional observation demonstrated that vesicles may be transported from the cytoplasm to the apical membrane of the podocytes. The increased protein bands in the gel electrophoresis of the sieved glomeruli of nephrotic rats were analyzed by mass spectrometry in comparison to the control rats. The major proteins increased in the nephrotic rats were cytoplasmic dynein 1 heavy chain, myosin IX, and myosin VIIb. In conclusion, the podocyte endocytic vesicles carrying albumin increased with glomerular cytoplasmic dynein and myosin in minimal change nephrotic rats.


Asunto(s)
Albúminas/metabolismo , Endocitosis , Síndrome Nefrótico/metabolismo , Podocitos/metabolismo , Vesículas Transportadoras/metabolismo , Albúminas/química , Animales , Dineínas Citoplasmáticas/metabolismo , Azul de Evans/química , Humanos , Inyecciones Intravenosas , Masculino , Miosinas/metabolismo , Síndrome Nefrótico/inducido químicamente , Síndrome Nefrótico/patología , Podocitos/patología , Isoformas de Proteínas/metabolismo , Puromicina Aminonucleósido , Ratas , Ratas Sprague-Dawley , Coloración y Etiquetado/métodos , Vesículas Transportadoras/química
7.
Med Mol Morphol ; 49(1): 48-52, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26141649

RESUMEN

In a case of acquired Fanconi syndrome associated with smoldering myeloma, we confirmed the deposition of protease-resistant κ light chain proteins in a proximal tubular injury and found the decreased expression of apical tubular transporters including sodium glucose co-transporter, sodium phosphate co-transporter, uric acid transporter 1, and a decrease of Na(+)/K(+)-ATPase in the basolateral membrane. The protease-resistant kappa light chain has a pathological role in the expression of tubular transporters in the proximal tubule and causes Fanconi syndrome associated with smoldering myeloma.


Asunto(s)
Síndrome de Fanconi/metabolismo , Cadenas kappa de Inmunoglobulina/metabolismo , Túbulos Renales Proximales/metabolismo , Síndrome de Fanconi/tratamiento farmacológico , Síndrome de Fanconi/etiología , Femenino , Humanos , Túbulos Renales Proximales/patología , Persona de Mediana Edad , Mieloma Múltiple/etiología , Mieloma Múltiple/metabolismo , Transportadores de Anión Orgánico/metabolismo , Proteínas de Transporte de Catión Orgánico/metabolismo , Osteomalacia/metabolismo , Péptido Hidrolasas/metabolismo , Transportador 2 de Sodio-Glucosa/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo
8.
Nephrology (Carlton) ; 20 Suppl 2: 101-4, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26031599

RESUMEN

Although membranous nephropathy (MN) is a commonly observed cause of post-transplant glomerulonephritis, distinguishing de novo from recurrent MN in kidney allograft is often difficult. Phospholipase A2 receptor (PLA2R) staining is useful for diagnosing recurrent MN in allografts similarly to idiopathic MN in native kidney. No specific treatment strategy has been established for MN, especially when accompanied with HCV infection in kidney transplant recipients. This report describes a 66-year-old man who was diagnosed as having PLA2R positive membranous nephropathy accompanied with already-known IgA nephropathy and HCV infection 26 years after kidney transplantation conducted between identical twins. PLA2R was detected along capillary loops, implying that this patient is affected by the same pathogenic mechanism as idiopathic MN, not secondary MN associated with other disorders such as HCV infection. The patient successfully achieved clinical remission after steroid therapy.


Asunto(s)
Enfermedades en Gemelos , Glomerulonefritis Membranosa/etiología , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Riñón/química , Donadores Vivos , Receptores de Fosfolipasa A2/análisis , Adulto , Anciano , Aloinjertos , Biomarcadores/análisis , Biopsia , Técnica del Anticuerpo Fluorescente , Glomerulonefritis por IGA/inmunología , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/tratamiento farmacológico , Glomerulonefritis Membranosa/inmunología , Glomerulonefritis Membranosa/metabolismo , Hepatitis C/inmunología , Humanos , Inmunosupresores/uso terapéutico , Riñón/efectos de los fármacos , Riñón/inmunología , Riñón/ultraestructura , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/inmunología , Trasplante de Riñón/métodos , Masculino , Microscopía Electrónica , Síndrome Nefrótico/etiología , Inducción de Remisión , Esteroides/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento
9.
Clin Exp Nephrol ; 18(1): 95-103, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23670304

RESUMEN

BACKGROUNDS: Podocytes are highly differentiated epithelial cells involved in glomerular filtration. This study determines the clinical and histological significance of podocyte detachment and excretion in urine in patients with chronic kidney diseases. METHODS: Renal biopsy was performed in 59 patients (30 males, 29 females; mean age 48 ± 2 years), including 24 patients with immunoglobulin (Ig)A nephropathy, six each with focal segmental glomerulosclerosis, membranous nephropathy, and minimal change nephrotic syndrome, and 17 with other renal disorders. The number of glomerular podocytes and severity of morphological damage were evaluated in renal biopsy samples. Urinary podocytes were detected by anti-human podocalyxin antibody. The urinary IgG/albumin ratio and urinary peroxide products were assessed by gel electrophoresis and the 2',7'-dichlorodihydrofluorescein-diacetate method, respectively. RESULTS: A decrease in glomerular podocytes was associated with age (r = -0.33; P < 0.05), glomerulosclerosis (r = -0.43; P < 0.01), tubulointerstitial lesions (r = -0.46; P < 0.01), and low estimated glomerular filtration rates (r = 0.32; P < 0.05). Increased urinary podocyte excretion correlated with proteinuria (r = 0.36; P < 0.01), and was observed more frequently in patients with active histological lesions. Podocyte loss correlated with lower selectivity of proteinuria in patients with minimal change nephrotic syndrome and focal segmental glomerulosclerosis (r = -0.90; P < 0.001). Moreover, urinary peroxide products increased in association with glomerulosclerosis (r = 0.39; P < 0.05). CONCLUSIONS: Urinary podocyte excretion reflects ongoing glomerular injury in various kidney diseases, and podocyte loss correlated with glomerulosclerosis and impaired selectivity of proteinuria.


Asunto(s)
Podocitos/patología , Insuficiencia Renal Crónica/patología , Orina/citología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Albuminuria/patología , Albuminuria/orina , Biomarcadores/orina , Biopsia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Peróxidos/orina , Podocitos/metabolismo , Valor Predictivo de las Pruebas , Pronóstico , Insuficiencia Renal Crónica/orina , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto Joven
10.
Biochem J ; 450(2): 295-301, 2013 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-23231444

RESUMEN

H(v) channels (voltage-gated proton channels) are expressed in blood cells, microglia and some types of epithelial cells. In neutrophils H(v) channels regulate the production of reactive oxygen species through regulation of membrane potential and intracellular pH. H(v) channels have also been suggested to play a role in sperm physiology in the human. However, the functions of the Hv channel at the whole-body level are not fully understood. In the present paper we show that Hvcn1 (voltage-gated hydrogen channel 1)-knockout mice show splenomegaly, autoantibodies and nephritis, that are reminiscent of human autoimmune diseases phenotypes. The number of activated T-cells was larger in Hvcn1-deficient mice than in the wild-type mice. Upon viral infection this was remarkably enhanced in Hvcn1-deficient mice. The production of superoxide anion in T-cells upon stimulation with PMA was significantly attenuated in the Hvcn1-deficient mice. These results suggest that H(v) channels regulate T-cell homoeostasis in vivo.


Asunto(s)
Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/metabolismo , Bombas de Protones/genética , Animales , Humanos , Activación del Canal Iónico , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neutrófilos/metabolismo , Fenotipo , Bombas de Protones/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Superóxidos/metabolismo , Linfocitos T/metabolismo
11.
Kidney Int ; 84(5): 861-3, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24172729

RESUMEN

The kidneys play an important role in protein metabolism. Renal tubules reabsorb 3 g of albumin under normal conditions, and exhibit a 6-fold increase in the reabsorption of albumin in patients with focal segmental glomerulosclerosis. The capacity of tubular lysosomal proteolysis can be increased up to 8-fold; however, proteinuria over the capacity of tubular handling may cause tubulointerstitial damage in patients with nephrotic syndrome.


Asunto(s)
Glomeruloesclerosis Focal y Segmentaria/enzimología , Túbulos Renales Proximales/enzimología , Lisosomas/enzimología , Péptido Hidrolasas/metabolismo , Animales
13.
J Med Case Rep ; 17(1): 549, 2023 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-38129918

RESUMEN

BACKGROUND: Crescentic glomerulonephritis with syphilis infection is rare, and the mechanism underlying the formation of glomerular capillary wall damage-induced crescent has not been elucidated. CASE PRESENTATION: A 62-year-old Japanese male showed edema, eruption, and rapid deterioration of the renal function after an acute syphilis infection. A renal biopsy showed crescentic glomerulonephritis with C3 deposition in the glomerular capillary wall, and immunostaining for anti-Treponema pallidum antibody was weakly positive in some interstitium and one glomerulus. Electron microscopy revealed the presence of string-shaped structures in the glomerular capillary walls. After treatment with penicillin followed by prednisolone, the renal function and urinary abnormalities, including Treponema pallidum protein, disappeared. CONCLUSIONS: Crescentic glomerulonephritis associated with syphilis showed a string-shaped deposition in the glomerular capillary and urinary Treponema pallidum protein excretion, and was effectively treated with penicillin and prednisolone.


Asunto(s)
Glomerulonefritis , Sífilis , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Aguda , Glomerulonefritis/complicaciones , Glomerulonefritis/tratamiento farmacológico , Glomérulos Renales/irrigación sanguínea , Glomérulos Renales/patología , Penicilinas/uso terapéutico , Prednisolona/uso terapéutico , Sífilis/complicaciones , Sífilis/diagnóstico , Sífilis/tratamiento farmacológico
14.
PLoS One ; 18(2): e0281770, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36780539

RESUMEN

A long-term high-fat diet (HFD) causes obesity and changes in renal lipid metabolism and lysosomal dysfunction in mice, causing renal damage. Sodium-glucose co-transporter inhibitors, including phlorizin, exert nephroprotective effects in patients with chronic kidney disease, but the underlying mechanism remains unclear. A HFD or standard diet was fed to adult C57BL/6J male mice, and phlorizin was administered. Lamellar body components of the proximal tubular epithelial cells (PTECs) were investigated. After phlorizin administration in HFD-fed mice, sphingomyelin and ceramide in urine and tissues were assessed and label-free quantitative proteomics was performed using kidney tissue samples. Mitochondrial elongation by fusion was effective in the PTECs of HFD-fed obese mice under phlorizin administration, and many lamellar bodies were found in the apical portion of the S2 segment of the proximal tubule. Phlorizin functioned as a diuretic, releasing lamellar bodies from the apical membrane of PTECs and clearing the obstruction in nephrons. The main component of the lamellar bodies was sphingomyelin. On the first day of phlorizin administration in HFD-fed obese mice, the diuretic effect was increased, and more sphingomyelin was excreted through urine than in vehicle-treated mice. The expressions of three peroxisomal ß-oxidation proteins involved in fatty acid metabolism were downregulated after phlorizin administration in the kidneys of HFD-fed mice. Fatty acid elongation protein levels increased with phlorizin administration, indicating an increase in long-chain fatty acids. Lamellar bodies accumulated in the proximal renal tubule of the S2 segment of the HFD-fed mice, indicating that the urinary excretion of lamellar bodies has nephroprotective effects.


Asunto(s)
Dieta Alta en Grasa , Simportadores , Masculino , Animales , Ratones , Dieta Alta en Grasa/efectos adversos , Ratones Obesos , Esfingomielinas , Florizina/farmacología , Ratones Endogámicos C57BL , Ácidos Grasos , Glucosa , Sodio
15.
Clin Transplant ; 26 Suppl 24: 76-80, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22747481

RESUMEN

A 64-yr-old man with end-stage kidney disease caused by hypertensive nephrosclerosis underwent living-unrelated ABO-identical kidney transplantation (KTx) at the age of 60 yr from his 60-yr-old wife. Maintenance trough concentration of cyclosporine A (CsA) was 100 ± 30 ng/mL. Five months after KTx, proteinuria gradually increased to around 1 g/d. TRBx at eight months after KTx revealed the new-onset alteration of mild arteriolosclerosis with intimal hyalinosis, which might reflect calcineurin inhibitor (CNI)-associated arteriopathy (CAA). Nearly one and half years after KTx, urinary protein excretion became nearly 2 g/d. TRBx revealed the advanced CAA and findings of focal segmental glomerulosclerosis (FSGS). Then, CNI was switched from CsA to tacrolimus (TAC). TRBx at two and half years after KTx revealed progressed arteriolar transmural thickening and striped fibrosis, which were supposed to be induced by an increase in serum TAC concentration because of acute enterocolitis. Then, TAC dose was reduced to serum trough concentration 5-8 ng/mL, but urinary protein excretion was increased up to 10 g/d. Reduction of TAC to trough concentration 2.0 ± 0.5 ng/mL reduced urinary protein excretion. Attempts to elevate TAC trough concentration within normal range (4-8 ng/mL) reproducibly induced the recurrence of an increase in sCr or urinary protein excretion. All these findings supported the etiology of graft dysfunction, and proteinuria of this case was FSGS.


Asunto(s)
Calcineurina/efectos adversos , Glomeruloesclerosis Focal y Segmentaria/etiología , Inmunosupresores/efectos adversos , Fallo Renal Crónico/complicaciones , Trasplante de Riñón/efectos adversos , Glomeruloesclerosis Focal y Segmentaria/patología , Humanos , Fallo Renal Crónico/tratamiento farmacológico , Masculino , Persona de Mediana Edad
16.
Int J Nephrol ; 2022: 2702651, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35866051

RESUMEN

Background: Urinary podocyte excretion is related to a reduction in glomerular podocyte numbers, glomerulosclerosis, and urinary protein selectivity. To elucidate the role of urinary podocytes in proteinuria and renal prognosis and to identify the factors that cause podocyte detachment, we examined urinary podocytes in 120 renal biopsy patients. Methods: Podocytes were identified in urinary sediments stained with fluorescent-labeled anti-podocalyxin antibodies in ten high power fields. The amounts of protein bands, separated by SDS-polyacrylamide gel electrophoresis, were calculated using an image software program and the correlation with urinary podocytes was analyzed. Podocyte surface pores were observed using a low-vacuum scanning electron microscope. The renal prognosis, including induction of hemodialysis or 30% reduction in eGFR, was investigated. Results: Urinary podocyte excretion showed a higher positive correlation with albumin excretion compared to IgG, prealbumin, and transferrin. There were no significant correlations between urinary podocyte count and low molecular weight proteins, including ß2-microglobulin and α1-microglobulin. The number of podocyte surface pores was positively correlated with proteinuria, suggesting enhanced albumin transcytosis. The hemodynamic pressure on the glomerular capillary wall, including products of pulse pressure and pulse rate (water hammer pressure), was positively correlated with urinary podocyte excretion. Urinary podocyte excretion and Tamm-Horsfall protein (THP) were independent risk factors for renal prognosis but were not related to response to treatment. Conclusion: Urinary podocyte excretion was correlated with urinary albumin excretion, indicating specific albumin transport by podocytes. Podocytes were detached from the glomerular capillaries by water hammer pressure and THP was involved in the renal prognosis.

17.
Vaccines (Basel) ; 10(9)2022 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-36146521

RESUMEN

A 16-year-old girl with no history of renal disease had a fever of 38 °C after her second HPV vaccination and was identified as positive for proteinuria. As she maintained urinary protein of 3.10 g/gCr and 5-9 urinary red blood cells/HPF, a renal biopsy was performed and small spikes on PAM staining with the granular deposition of IgG1++ and IgG3+ on the glomerular capillary wall were discovered by immunofluorescence, although PLA2R immunostaining was negative. Analysis by electron microscope showed electron density deposition in the form of fine particles under the epithelium. The diagnosis was secondary membranous nephropathy stage II. Immunostaining with the anti-p16 INK4a antibody was positive for glomerular cells, and Western blot analysis of urinary protein showed a positive band for p16 INK4a. However, laser-microdissection mass spectrometry analysis of a paraffin section of glomeruli failed to detect HPV proteins. It is possible that the patient was already infected with HPV and administration of the HPV vaccine may have caused secondary membranous nephropathy.

18.
Intern Med ; 61(6): 871-876, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35296622

RESUMEN

A 70-year-old woman with complaints of edema, general malaise, and hypotension was diagnosed with renal amyloidosis, and laser microdissection mass spectrometry revealed her amyloidosis to predominantly comprise the apolipoprotein A-IV type. The M-protein turned from negative to positive during the course, and a bone marrow biopsy showed smoldering myeloma. Treatment with bortezomib and dexamethasone failed to save her from heart failure six months after the onset. Western blotting of urine samples at the time of the renal biopsy showed that amyloid light-chain κ amyloidosis had been present since the onset. Unlike the myeloma, Congo red staining was positive in the plasma cells of the bone marrow.


Asunto(s)
Amiloidosis , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Mieloma Múltiple , Anciano , Amiloidosis/complicaciones , Amiloidosis/diagnóstico , Amiloidosis/patología , Apolipoproteínas A , Femenino , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/complicaciones , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/diagnóstico , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/tratamiento farmacológico , Mieloma Múltiple/diagnóstico
20.
Kidney Int ; 80(12): 1328-38, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21849973

RESUMEN

The mechanism of selective albuminuria in minimal change nephrotic syndrome, in which glomerular capillaries are diffusely covered by effaced podocyte foot processes with reduced slit diaphragms, is unknown. Podocyte injury is due, in part, to NADPH-induced oxidative stress. Here we studied mechanism of selective albuminuria in puromycin aminonucleoside (PAN) nephrotic rats, a model of minimal change nephrotic syndrome. In these rats, Evans Blue-labeled human albumin was taken up by podocytes and its urinary excretion markedly increased, with retained selectivity for albumin. Immunogold scanning electron micrographic images found increased human albumin in podocyte vesicles and on the apical membrane in nephrotic compared with control rats. Apocynin, an inhibitor of NADPH oxidase, decreased superoxide production in podocytes, and inhibited endocytosis and urinary albumin excretion. Real-time confocal microscopy found an initial delay in the appearance of Evans Blue-labeled human albumin in the tubular lumen, reflecting the time needed for transcellular transport. Immunoprecipitation analysis indicated that FcRn, a receptor for albumin transport, mediated podocyte albumin transport, and treatment with anti-FcRn antibody reduced proteinuria in these nephrotic rats. Thus, podocyte albumin transport was enhanced in PAN nephrotic rats by means of FcRn, which may explain the mechanism of selective proteinuria. This was blocked by apocynin, suggesting a new therapeutic approach.


Asunto(s)
Acetofenonas/farmacología , Albuminuria/prevención & control , Inhibidores Enzimáticos/farmacología , NADPH Oxidasas/antagonistas & inhibidores , Nefrosis Lipoidea/tratamiento farmacológico , Podocitos/efectos de los fármacos , Puromicina , Albúmina Sérica/metabolismo , Albuminuria/inducido químicamente , Albuminuria/enzimología , Albuminuria/patología , Albuminuria/orina , Animales , Transporte Biológico , Modelos Animales de Enfermedad , Endocitosis/efectos de los fármacos , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Inmunohistoquímica , Inmunoprecipitación , Cinética , Masculino , Microscopía Confocal , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , NADPH Oxidasas/metabolismo , Nefrosis Lipoidea/inducido químicamente , Nefrosis Lipoidea/enzimología , Nefrosis Lipoidea/patología , Nefrosis Lipoidea/orina , Estrés Oxidativo/efectos de los fármacos , Podocitos/enzimología , Podocitos/ultraestructura , Ratas , Ratas Endogámicas Lew , Ratas Sprague-Dawley , Ratas Transgénicas , Especies Reactivas de Oxígeno/metabolismo , Receptores Fc/metabolismo
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