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Immunologic Mechanisms in Renal Disease
Published in Robin S. Goldstein, Mechanisms of Injury in Renal Disease and Toxicity, 2020
Brian D. Schreiber, Gerald C. Groggel
Rats immunized with a tubular basement membrane (TBM) preparation can develop anti-TBM antibodies similar to those seen in anti-GBM nephritis (Wilson, 1989). The antibodies are associated with an interstitial nephritis. Tamm-Horsfall protein is found in certain cells along the nephron and can act as an antigen to form immune deposits and interstitial nephritis. Certain strains, such as Lewis rats, lack the TBM antigen. When immunized with TBM antigen they develop a cellular immune interstitial nephritis without Ig (Bannister et al., 1987). This lesion can be easily transferred with immune cells. Thus the tubulointerstitial areas of kidney can be the site at which both humoral and cellular components of the immune system produce immunologic injury.
Renal Pathophysiology
Published in Manit Arya, Taimur T. Shah, Jas S. Kalsi, Herman S. Fernando, Iqbal S. Shergill, Asif Muneer, Hashim U. Ahmed, MCQs for the FRCS(Urol) and Postgraduate Urology Examinations, 2020
Herman S. Fernando, Mohamed Yehia Abdallah, Iqbal S. Shergill
Which of the following is TRUE regarding biochemical pathology of urine?Tamm-Horsfall protein is secreted by renal epithelial cells in the loop of Henle and the proximal convoluted tubule as a membrane-anchored protein.Nephrocalcin is an acidic glycoprotein containing predominantly acidic amino acids that is synthesised in the thick ascending limb and distal tubule.Uropontin is an acidic phosphorylated glycoprotein expressed in bone matrix and renal epithelial cells of the ascending limb of the loop of Henle and the distal tubule.Polyanions including glycosaminoglycans, acid mucopolysaccharides and RNA have been shown to inhibit crystal growth but not nucleation.Among the glycosaminoglycans, heparan sulfate interacts most strongly with calcium phosphate crystals.
The kidneys
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Microdissection studies have shown the presence of long hyaline tubular casts, consisting largely of Tamm–Horsfall protein, which must restrict tubular flow. This is associated with raised intratubular pressure and dilated tubular lumina. The diuretic phase of acute tubular necrosis is associated with a great increase in Tamm–Horsfall protein in the urine and may indicate the flushing out of these casts. Tubular constriction also leads to afferent arteriolar vasoconstriction, which further lowers the filtration pressure gradient. Protein casts and dilated tubules are, however, found in the recovery phase of ATN and hence tubular obstruction cannot be the whole story.
Expression of NEDD4L and ENaC in Urinary Extracellular Vesicles in Pre-eclampsia
Published in Hypertension in Pregnancy, 2023
P.Y.M. Leung, M Katerelos, S. Choy, N Cook, M Lee, K Paizis, A Abboud, J. A. Manning, P.F Mount, D.A Power
A limitation of this study is the small sample size. There were four urine samples which yielded negative vesicles markers, despite repeating the separation process twice. These samples had relatively low urine creatinine indicating these were more dilute and were likely to have a lower concentration of UEV. Additionally, Blijdorp et al. detected more Tamm-Horsfall protein in dilute urine, which generated more Tamm-Horsfall protein oligomers and interfered with the detection of UEV (20). In the other samples, the vesicle markers TSG101 and CD9 were reliably detected, which supported the presence of UEV after the separation process. Further investigation such as with a larger study population would help identify any relationship between NEDD4L and α-ENaC. This would also enable comparisons between different clinical presentations of pre-eclampsia, such as early-onset versus term pre-eclampsia, and mild versus severe disease. The current study excluded participants with baseline renal disease or diabetes; however, analysis of NEDD4L and ENaC in these subgroups would provide interesting insights. Although there was no statistical difference in body mass index between the groups, future studies could examine whether pre-pregnancy obesity impacts ENaC and NEDD4L expression in pre-eclampsia.
On the protein content of kidney stones: an explorative study
Published in Acta Clinica Belgica, 2022
Mieke Steenbeke, Marc L. De Buyzere, Marijn M. Speeckaert, Joris R. Delanghe
Modern literature no longer regards urinary proteins as an innocent bystander in urolithiasis, but more and more highlights their role [5, 6]. Crystal nucleation, growth, aggregation in urine and crystal attachment to renal epithelial cells depend upon the modulatory compounds in renal environment [3]. Tamm-Horsfall protein (THP) or uromodulin, a 90-kDa protein, produced in the kidney by the epithelial cells lining the thick ascending limb of the loop of Henle and early distal tubules, is the most abundant protein in healthy urine [7–10]. Proteomics analyses have been carried out in previous published studies on calcium oxalate, calcium phosphate and uric acid kidney stones, with the characterization of hundreds of proteins [4, 11–13]. This for a better understanding of the kidney stone matrix protein composition and the molecular mechanisms for kidney stone formation to improve management of kidney stone disease [11–13]. Recent kidney stone research has indicated critical roles of a group of proteins, namely stone modulatory proteins, which can act as stone promotors or inhibitors [4]. Given the growing insight that urinary proteins play a major role in stone formation [14], there may be an increasing interest in detecting the relative expression of proteins in kidney stones by ATR-FTIR spectroscopy.
Rotula aquatica Lour. mitigates oxidative stress and inflammation in acute pyelonephritic rats
Published in Archives of Physiology and Biochemistry, 2022
A. Vysakh, Kuriakose Jayesh, Ninan Jisha, V. Vijeesh, Sebastian Jose Midhun, Mathew Jyothis, M. S. Latha
Tamm Horsfall protein is an important glycoprotein found in human urine. It is also known as uromodulin, which binds to type 1 fimbriae and thus controlling the interaction of uropathogenic E. coli with host receptors (Serafini-Cessi et al.2003). The uromodulin concentration gives a clear idea about the number of functional nephrons/renal tissues/tubular secretion (Steubl et al.2016). The decreased level of uromodulin was observed in early stages of tubular function impairment. Thus, it is considered as an early and direct marker of kidney disorders. Researchers observed that the uromodulin exhibited a linear correlation with estimated glomerular filtration rate (eGFR) while other markers (creatinine, blood urea nitrogen (BUN), and cystatin C) represent a hyperbolic correlation to eGFR (Steubl et al.2016). The level of THP proteins was reduced during the acute pyelonephritis. The downregulated expression of THP was upregulated by the administration of MERA at different doses. These observations prove the efficacy of MERA for preventing the uropathogenic E. coli from interacting with host receptors. This capability of MERA should reduce the pathogen attack and infection associated with pyelonephritis.