Urine proteome of autosomal dominant polycystic kidney disease patients

Bakun, Magda; Niemczyk, Mariusz; Domański, Dominik; Jaźwiec, Radosław; Perzanowska, Anna; Niemczyk, Stanisław; Kistowski, Michał; Fabijańska, Agnieszka; Borowiec, Agnieszka; Pączek, Leszek; Dadlez, Michał

doi:10.1186/1559-0275-9-13

Cited by 49 publications

(46 citation statements)

References 22 publications

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“…Increased concentrations of complement proteins, including C3, Factor B and C9, can also be found in the urine and by immunostaining along the cyst epithelium, suggesting activation of the alternative pathway [59,61] . Song et al [62] described the pattern of gene expression in ADPKD kidneys.…”

Section: Polycystic Kidney Diseasementioning

confidence: 99%

Complement activation in progressive renal disease

Fearn

Sheerin

2015

WJN

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ritis, thrombotic microangiopathies and transplant reje ction. In this review we discuss current evidence that complement activation contributes to progression of CKD, how complement could cause renal inflammation and whether complement inhibition would slow progression of renal disease. Core tip: Complement activation occurs in progressive chronic kidney disease and may contribute to the chronic inflammation that is characteristically found in the kidney. It is therefore possible that inhibiting complement activation would reduce inflammation, lead to reduced fibrosis and preservation of renal function. INTRODUCTIONChronic kidney disease (CKD) is recognised worldwide as a major public health problem [1] . In 2007 the United Kingdom age-standardised prevalence of CKD stages 3-5 was 8.5% (10.6% in females and 5.8% in males) [2] and similar prevalences have been described in other countries. In 2012 in the United Kingdom, the number of new patients requiring renal replacement therapy was 6891, equating to 108 patients per million population, with diabetes and glomerulonephritis being the two most common diagnoses in incident dialysis patients. Although not all patients with CKD will progress to renal failure, all stages of CKD are associated with increased AbstractChronic kidney disease (CKD) is common and the cause of significant morbidity and mortality. The replacement of functioning nephrons by fibrosis is characteristic of progressive disease. The pathways that lead to fibrosis are not fully understood, although chronic nonresolving inflammation in the kidney is likely to drive the fibrotic response that occurs. In patients with progressive CKD there is histological evidence of inflammation in the interstitium and strategies that reduce inflammation reduce renal injury in preclinical models of CKD. The complement system is an integral part of the innate immune system but also augments adaptive immune responses. Complement activation is known to occur in many diverse renal diseases, including glomeruloneph morbidity and mortality [1] . Tubulointerstitial inflammation and fibrosis is a major factor in the progressive loss of renal function in most kidney diseases [3] . The process is complex due to the number of interacting pathways which ultimately result in the replacement of functioning nephrons with scar tissue. Cellular stress and injury induces an inflammatory and pro-fibrogenic response involving growth factors [4][5][6] and pro-inflammatory cytokines as well as activation of the renin-angiotensin system. This leads to a chronic inflammatory cell infiltrate, increasing numbers of activated fibroblasts (myofibroblasts) and excessive matrix deposition. There is evidence from preclinical models that the immune system is important in the development of renal fibrosis [7,8] . A component of the innate immune system that may be important in driving renal inflammation is the complement system, which can directly affect cell function and also influence the adaptive immune response. REVIEW COMPLEMENT SYSTEMTh...

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Section: Polycystic Kidney Diseasementioning

confidence: 99%

Complement activation in progressive renal disease

Fearn

Sheerin

2015

WJN

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“…We still do not know how most of the studied markers behave in the above condi tions, let alone others. While acknowledging the results of studies published so far, including our own studies, 4,5,9,[12][13][14] there is still a clear need for integration of these results.…”

Section: 5mentioning

confidence: 94%

How to diagnose and follow patients with glomerulonephritis without kidney biopsy?

Mucha¹,

Foroncewicz²,

Pączek³

2016

Polish Archives of Internal Medicine

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“…The UPLC system was interfaced with the quadrupole micro‐time‐of‐flight MS electrospray ionization ion source of the Orbitrap Elite type mass spectrometer (Thermo Fisher Scientific, Waltham, MA, USA) working in the regimen of data dependent MS to MS/MS switch with higher collisional dissociation type peptide fragmentation (28). An electrospray voltage of 2 kV was used.…”

Section: Methodsmentioning

confidence: 99%

N‐Homocysteinylation impairs collagen cross‐linking in cystathionine β‐synthase‐deficient mice: a novel mechanism of connective tissue abnormalities

et al. 2016

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Cystathionine β-synthase (CBS) deficiency, a genetic disorder in homocysteine (Hcy) metabolism in humans, elevates plasma Hcy-thiolactone and leads to connective tissue abnormalities that affect the cardiovascular and skeletal systems. However, the underlying mechanism of these abnormalities is not understood. Hcy-thiolactone has the ability to form isopeptide bonds with protein lysine residues, which generates N-homocysteinylated protein. Because lysine residues are involved in collagen cross-linking, N-homocysteinylation of these lysines should impair cross-linking. Using a Tg-I278T Cbs mouse model of hyperhomocysteinemia (HHcy) which replicates the connective tissue abnormalities observed in CBS-deficient patients, we found that N-Hcy-collagen was elevated in bone, tail, and heart of Cbs mice, whereas pyridinoline cross-links were significantly reduced. Plasma deoxypyridinoline cross-link and cross-linked carboxyterminal telopeptide of type I collagen were also significantly reduced in the Cbs mice. Lysine oxidase activity and mRNA level were not reduced by the Cbs genotype. We also showed that collagen carries S-linked Hcy bound to the thiol of N-linked Hcy. In vitro experiments showed that Hcy-thiolactone modifies lysine residues in collagen type I α-1 chain. Residue K, located in the nonhelical N-telopeptide region and involved in pyridinoline cross-link formation, was also N-homocysteinylated in vivo Taken together, our findings showed that N-homocysteinylation of collagen in Cbs mice impairs its cross-linking. These findings explain, at least in part, connective tissue abnormalities observed in HHcy.-Perła-Kajan, J., Utyro, O., Rusek, M., Malinowska, A., Sitkiewicz, E., Jakubowski, H. N-Homocysteinylation impairs collagen cross-linking in cystathionine β-synthase-deficient mice: a novel mechanism of connective tissue abnormalities.

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Urine proteome of autosomal dominant polycystic kidney disease patients

Cited by 49 publications

References 22 publications

Complement activation in progressive renal disease

Complement activation in progressive renal disease

How to diagnose and follow patients with glomerulonephritis without kidney biopsy?

N‐Homocysteinylation impairs collagen cross‐linking in cystathionine β‐synthase‐deficient mice: a novel mechanism of connective tissue abnormalities

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