A well-developed endolysosomal system reflects protein reabsorption in segment 1 and 2 of rat proximal tubules

2020 ◽  
Author(s):  
Erik I. Christensen ◽  
Inger B. Kristoffersen ◽  
Birgitte Grann ◽  
Jesper S. Thomsen ◽  
Arne Andreasen ◽  
...  
Keyword(s):  
Proximal Tubules ◽  
Protein Reabsorption

scholarly journals Antiproteinuric Therapy while Preventing the Abnormal Protein Traffic in Proximal Tubule Abrogates Protein- and Complement-Dependent Interstitial Inflammation in Experimental Renal Disease

1999 ◽  
Vol 10 (4) ◽  
pp. 804-813
Author(s):  
MAURO ABBATE ◽  
CARLA ZOJA ◽  
DANIELA ROTTOLI ◽  
DANIELA CORNA ◽  
NORBERTO PERICO ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Proximal Tubules ◽  
Complement C3 ◽  
Abnormal Protein ◽  
Protein Traffic ◽  
Tubular Cells ◽  
Mhc Ii ◽  
Interstitial Inflammation ◽  
Proximal Tubular ◽  
Protein Reabsorption

Abstract. In proteinuric glomerulopathies, the excess traffic of proteins into the renal tubule is a candidate trigger of interstitial inflammatory and immune events leading to progressive injury, and a key target for the renoprotective action of antiproteinuric drugs. Among proteins trafficked to the proximal tubule, the third component of complement (C3) can be activated locally and contribute to inflammation at sites of protein reabsorption. Experiments were performed in rats with renal mass reduction (RMR, 5/6 nephrectomy) with the following aims: (1) to study Ig (IgG) and complement deposition in proximal tubules, and interstitial macrophage infiltration and MHC class II expression at intervals after surgery by double immunofluorescence analysis; (2) to assess whether lisinopril (angiotensin-converting enzyme inhibitor [ACEi], 25 mg/L in the drinking water, from either day 1 or day 7) limited IgG and C3 accumulation and interstitial inflammation at day 30. In 7-d remnant kidneys, intracellular staining for both IgG and C3 was detectable in proximal tubules in focal areas; C3 was restricted to IgG-positive tubular cells, and there were no interstitial ED-1 macrophage and MHC II-positive cellular infiltrates. In 14-d and 30-d remnant kidneys, proximal tubular IgG and C3 staining was associated with the appearance of interstitial infiltrates that preferentially localized to areas of tubules positive for both proteins. RMR rats given ACEi had no or limited increases in levels of urinary protein excretion, tubular IgG, and C3 reactivity, and interstitial cellular infiltrates in kidneys at 30 d, even when ACEi was started from day 7 after surgery. These findings document that (1) in RMR, IgG and C3 accumulation in proximal tubular cells is followed by leukocyte infiltration and MHC II overexpression in the adjacent interstitium; (2) ACEi while preventing proteinuria limits both tubular accumulation of IgG and C3 and interstitial inflammation. The data suggest that ACE inhibition can be renoprotective by limiting the early abnormal protein traffic in proximal tubule and consequent deleterious effects of excess protein reabsorption, including the accumulation and local activation of complement as well as the induction of chemokines and endothelin genes known to promote interstitial inflammation and fibrosis.

Reduction of Potassium in Kidney Proximal Tubules to Aid in Electron Probe X-Ray Microanalysis of Calcium

1985 ◽  
Vol 43 ◽  
pp. 474-475
Author(s):  
A. LeFurgey ◽  
P. Ingram ◽  
L.J. Mandel
Keyword(s):  
Smooth Muscle ◽  
Proximal Tubule ◽  
Electron Probe ◽  
Clinical Applications ◽  
Proximal Tubules ◽  
Rabbit Kidney ◽  
Target Cells ◽  
X Ray ◽  
Freeze Dried

For quantitative determination of subcellular Ca distribution by electron probe x-ray microanalysis, decreasing (and/or eliminating) the K content of the cell maximizes the ability to accurately separate the overlapping K Kß and Ca Kα peaks in the x-ray spectra. For example, rubidium has been effectively substituted for potassium in smooth muscle cells, thus giving an improvement in calcium measurements. Ouabain, a cardiac glycoside widely used in experimental and clinical applications, inhibits Na-K ATPase at the cell membrane and thus alters the cytoplasmic ion (Na,K) content of target cells. In epithelial cells primarily involved in active transport, such as the proximal tubule of the rabbit kidney, ouabain rapidly (t1/2= 2 mins) causes a decrease2 in intracellular K, but does not change intracellular total or free Ca for up to 30 mins. In the present study we have taken advantage of this effect of ouabain to determine the mitochondrial and cytoplasmic Ca content in freeze-dried cryosections of kidney proximal tubule by electron probe x-ray microanalysis.

Renal Protective Effects of Empagliflozin via Inhibition of the EMT Program Associated with Suppression of Aberrant Glycolysis in Proximal Tubules

2019 ◽  
Author(s):  
Jinpeng Li ◽  
Susumu Takagi ◽  
Kyoko Nitta ◽  
Munehiro Kitada ◽  
Swayam P. Srivastava ◽  
...  
Keyword(s):  
Proximal Tubules ◽  
Protective Effects

scholarly journals Structural requirements for protection by small amino acids against hypoxic injury in kidney proximal tubules 1

1990 ◽  
Vol 4 (15) ◽  
pp. 3347-3354 ◽  
Author(s):  
Joel M. Weinberg ◽  
Manjeri A. Venkatachalam ◽  
Ricardo Garzo‐Quintero ◽  
Nancy F. Roeser ◽  
Julie A. Davis
Keyword(s):  
Amino Acids ◽  
Proximal Tubules ◽  
Structural Requirements ◽  
Hypoxic Injury ◽  
Kidney Proximal Tubules

scholarly journals Effect of Insulin on Proximal Tubules Handling of Glucose: A Systematic Review

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Ricardo Pereira-Moreira ◽  
Elza Muscelli
Keyword(s):  
Glucose Transport ◽  
Insulin Action ◽  
Current Knowledge ◽  
Sglt2 Inhibitor ◽  
Proximal Tubules ◽  
Human Studies ◽  
Glucose Disposal ◽  
Diabetic Patients ◽  
Insulin Effect ◽  
Renal Gluconeogenesis

Renal proximal tubules reabsorb glucose from the glomerular filtrate and release it back into the circulation. Modulation of glomerular filtration and renal glucose disposal are some of the insulin actions, but little is known about a possible insulin effect on tubular glucose reabsorption. This review is aimed at synthesizing the current knowledge about insulin action on glucose handling by proximal tubules. Method. A systematic article selection from Medline (PubMed) and Embase between 2008 and 2019. 180 selected articles were clustered into topics (renal insulin handling, proximal tubule glucose transport, renal gluconeogenesis, and renal insulin resistance). Summary of Results. Insulin upregulates its renal uptake and degradation, and there is probably a renal site-specific insulin action and resistance; studies in diabetic animal models suggest that insulin increases renal SGLT2 protein content; in vivo human studies on glucose transport are few, and results of glucose transporter protein and mRNA contents are conflicting in human kidney biopsies; maximum renal glucose reabsorptive capacity is higher in diabetic patients than in healthy subjects; glucose stimulates SGLT1, SGLT2, and GLUT2 in renal cell cultures while insulin raises SGLT2 protein availability and activity and seems to directly inhibit the SGLT1 activity despite it activating this transporter indirectly. Besides, insulin regulates SGLT2 inhibitor bioavailability, inhibits renal gluconeogenesis, and interferes with Na+K+ATPase activity impacting on glucose transport. Conclusion. Available data points to an important insulin participation in renal glucose handling, including tubular glucose transport, but human studies with reproducible and comparable method are still needed.

scholarly journals Development of osmotic vacuolization of proximal tubular epithelial cells following treatment with sodium-glucose transport protein 2 inhibitors in type II diabetes mellitus patients-3 case reports

2021 ◽  
Author(s):  
Shun Watanabe ◽  
Naoki Sawa ◽  
Hiroki Mizuno ◽  
Masayuki Yamanouchi ◽  
Tatsuya Suwabe ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Type Ii Diabetes ◽  
Sglt2 Inhibitor ◽  
Type Ii Diabetes Mellitus ◽  
Proximal Tubules ◽  
Type Ii ◽  
Tubular Epithelial Cells ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
Standard Weight

AbstractWe encountered 3 cases of acute kidney injury that occurred after treatment with a SGLT2 inhibitor. In case 1, serum creatinine increased from 1.65 to 3.0 mg/dL, in case 2, serum creatinine increased from 1.03 to 1.21 mg/dL, and in case 3, serum creatinine increased from 0.8 to 1.1 mg/dL. Renal biopsy showed isometric vacuolization on tubules, that was completely negative for Periodic acid-Schiff (PAS) stain in case 1, and was partially negative for PAS stain in case 2 and 3, consistent with osmotic vacuolization. Immunohistochemical analysis showed positive staining for CD138 and CD10 indicating the proximal tubules in the vacuolar lesions. 3 patients were obese with body mass index of more than 30, and showed an increase in serum renin. In conclusion, in type II diabetes mellitus (T2DM), individuals that remain within their standard weight range, SGLT2 inhibitor treatment does not result in osmotic vacuolization of proximal tubular epithelial cells and AKI. However, treatment with a SGLT2 inhibitor may cause damage of the proximal tubules resulting in AKI in T2DM individuals who do not remain within their standard weight range, due to an overdose lavage of sugar in the urine and dehydration.

scholarly journals The Prevalence of Inorganic Mercury in Human Kidneys Suggests a Role for Toxic Metals in Essential Hypertension

Toxics ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 67
Author(s):  
Roger Pamphlett ◽  
Philip A. Doble ◽  
David P. Bishop
Keyword(s):  
Essential Hypertension ◽  
Toxic Metals ◽  
Inductively Coupled Plasma ◽  
Dominant Role ◽  
Inorganic Mercury ◽  
Experimental Studies ◽  
Human Kidney ◽  
Proximal Tubules ◽  
Age Related ◽  
Icp Ms

The kidney plays a dominant role in the pathogenesis of essential hypertension, but the initial pathogenic events in the kidney leading to hypertension are not known. Exposure to mercury has been linked to many diseases including hypertension in epidemiological and experimental studies, so we studied the distribution and prevalence of mercury in the human kidney. Paraffin sections of kidneys were available from 129 people ranging in age from 1 to 104 years who had forensic/coronial autopsies. One individual had injected himself with metallic mercury, the other 128 were from varied clinicopathological backgrounds without known exposure to mercury. Sections were stained for inorganic mercury using autometallography. Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was used on six samples to confirm the presence of autometallography-detected mercury and to look for other toxic metals. In the 128 people without known mercury exposure, mercury was found in: (1) proximal tubules of the cortex and Henle thin loops of the medulla, in 25% of kidneys (and also in the man who injected himself with mercury), (2) proximal tubules only in 16% of kidneys, and (3) Henle thin loops only in 23% of kidneys. The age-related proportion of people who had any mercury in their kidney was 0% at 1–20 years, 66% at 21–40 years, 77% at 41–60 years, 84% at 61–80 years, and 64% at 81–104 years. LA-ICP-MS confirmed the presence of mercury in samples staining with autometallography and showed cadmium, lead, iron, nickel, and silver in some kidneys. In conclusion, mercury is found commonly in the adult human kidney, where it appears to accumulate in proximal tubules and Henle thin loops until an advanced age. Dysfunctions of both these cortical and medullary regions have been implicated in the pathogenesis of essential hypertension, so these findings suggest that further studies of the effects of mercury on blood pressure are warranted.

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