scholarly journals Molecular Mapping of Urinary Complement Peptides in Kidney Diseases

Proteomes ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 49
Author(s):  
Ralph Wendt ◽  
Justyna Siwy ◽  
Tianlin He ◽  
Agnieszka Latosinska ◽  
Thorsten Wiech ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Complement Activation ◽  
Molecular Mapping ◽  
Kidney Diseases ◽  
Positive Association ◽  
Inverse Association ◽  
Disease Etiology ◽  
Complement Proteins ◽  
Non Invasive ◽  
Therapeutic Decisions

Defective complement activation has been associated with various types of kidney disease. This led to the hypothesis that specific urine complement fragments may be associated with kidney disease etiologies, and disease progression may be reflected by changes in these complement fragments. We investigated the occurrence of complement fragments in urine, their association with kidney function and disease etiology in 16,027 subjects, using mass spectrometry based peptidomics data from the Human Urinary Proteome/Peptidome Database. Twenty-three different urinary peptides originating from complement proteins C3, C4 and factor B (CFB) could be identified. Most C3-derived peptides showed inverse association with estimated glomerular filtration rate (eGFR), while the majority of peptides derived from CFB demonstrated positive association with eGFR. Several peptides derived from the complement proteins C3, C4 and CFB were found significantly associated with specific kidney disease etiologies. These peptides may depict disease-specific complement activation and could serve as non-invasive biomarkers to support development of complement interventions through assessing complement activity for patients’ stratification and monitoring of drug impact. Further investigation of these complement peptides may provide additional insight into disease pathophysiology and could possibly guide therapeutic decisions, especially when targeting complement factors.

scholarly journals Differential excretion of urinary complement fragments in kidney diseases: a potential link to complement activation?

2021 ◽  
Author(s):  
Ralph Wendt ◽  
Justyna Siwy ◽  
Angnieszka Latosinska ◽  
Tianlin He ◽  
Harald Rupprecht ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Complement Activation ◽  
Kidney Diseases ◽  
Membranous Glomerulonephritis ◽  
Positive Association ◽  
Inverse Association ◽  
Disease Etiology ◽  
Complement Proteins ◽  
Therapeutic Decisions ◽  
Potential Link

Defective Complement activation has been associated with various types of kidney disease. This led to the hypothesis that specific urine complement fragments may be associated with kidney disease etiologies, and disease progression may be reflected by changes in these complement fragments. Therefore, we investigated the occurrence of complement fragments in urine, their association with kidney function and disease etiology. Mass spectrometry based peptidomics data from the Human Urinary Proteome/Peptidome Database were extracted and the distribution of complement peptides in the different kidney disease etiologies and controls was investigated. All datasets where information on disease/health status was available and at least one complement peptide could be detected were included (n=16027). Twenty-three different urinary peptides derived from complement proteins could be identified, originating from the complement proteins C3, C4 and CFB. For most C3-derived peptides an inverse association with eGFR was observed, while the majority of peptides derived from CFB demonstrated positive association with eGFR. Highest levels of significant C3 excretion relative to controls were seen in minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MGN), lupus nephritis (LN), diabetic kidney disease (DKD), IgAN, membranoproliferative glomerulonephritis (MPGN), and C3-glomerulonephritis. In conclusion, several peptides derived from the complement proteins C3, C4 and Factor B are significantly associated with specific kidney disease etiologies. These peptides may depict disease-specific complement activation, as well as damage to the glomerular basement membrane. Further investigation of these complement peptides may provide additional insight into disease pathophysiology and could possibly guide therapeutic decisions, especially when targeting complement factors.

scholarly journals Thyroid function, renal events and mortality in chronic kidney disease patients: the German Chronic Kidney Disease study

2020 ◽  
Author(s):  
Ulla T Schultheiss ◽  
Inga Steinbrenner ◽  
Matthias Nauck ◽  
Markus P Schneider ◽  
Fruzsina Kotsis ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Thyroid Function ◽  
Positive Association ◽  
Inverse Association ◽  
All Cause Mortality ◽  
Disease Study ◽  
Reduced Kidney Function

Abstract Background Hypothyroidism and low free triiodothyronine (FT3) syndrome [low FT3 levels with normal thyroid-stimulating hormone (TSH)] have been associated with reduced kidney function cross-sectionally in chronic kidney disease (CKD) patients with severely reduced estimated glomerular filtration rate (eGFR) or end-stage kidney disease (ESKD). Results on the prospective effects of impaired thyroid function on renal events and mortality for patients with severely reduced eGFR or from population-based cohorts are conflicting. Here we evaluated the association between thyroid and kidney function with eGFR (cross-sectionally) as well as renal events and mortality (prospectively) in a large, prospective cohort of CKD patients with mild to moderately reduced kidney function. Methods Thyroid markers were measured among CKD patients from the German Chronic Kidney Disease study. Incident renal endpoints (combined ESKD, acute kidney injury and renal death) and all-cause mortality were abstracted from hospital records and death certificates. Time to first event analysis of complete data from baseline to the 4-year follow-up (median follow-up time 4.04 years) of 4600 patients was conducted. Multivariable linear regression and Cox proportional hazards models were fitted for single and combined continuous thyroid markers [TSH, free thyroxine (FT4), FT3] and thyroid status. Results Cross-sectionally, the presence of low-FT3 syndrome showed a significant inverse association with eGFR and continuous FT3 levels alone showed a significant positive association with eGFR; in combination with FT4 and TSH, FT3 levels also showed a positive association and FT4 levels showed a negative association with eGFR. Prospectively, higher FT4 and lower FT3 levels were significantly associated with a higher risk of all-cause mortality (Nevents = 297). Per picomole per litre higher FT3 levels the risk of reaching the composite renal endpoint was 0.73-fold lower (95% confidence interval 0.65–0.82; Nevents = 615). Compared with euthyroid patients, patients with low-FT3 syndrome had a 2.2-fold higher risk and patients with hypothyroidism had a 1.6-fold higher risk of experiencing the composite renal endpoint. Conclusions Patients with mild to moderate CKD suffering from thyroid function abnormalities are at an increased risk of adverse renal events and all-cause mortality over time.

P0106URINE COMPLEMENT FRAGMENTS ARE ASSOCIATED WITH KIDNEY FUNCTION AND DISEASE ETIOLOGY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Tianlin He ◽  
Joachim Beige ◽  
Justyna Siwy ◽  
Igor Golovko ◽  
Martin Pejchinovski ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Function ◽  
Positive Association ◽  
P Value ◽  
Normal Kidney ◽  
Peptide Fragments ◽  
Disease Etiology ◽  
Complement Factors ◽  
Normal Kidney Function ◽  
Specific Distribution

Abstract Background and Aims Changes in complement factors have been associated with chronic kidney disease, most prominently in the context of C3 glomerulopathy. Based on these reports, the hypothesis was generated that specific urine complement fragments are associated with kidney disease etiologies, and progression of the disease may be reflected by changes in these proteins or peptides. In this study, we aimed at investigating the occurrence of complement fragments in urine, and their association with kidney function in general and disease etiology in particular. Methods Urine samples from patients with kidney disease of different etiologies and control subjects with normal kidney function were investigated using tandem mass spectrometry coupled with capillary electrophoresis and liquid chromatography to identify complement derived peptides based on their amino acid sequence. Subsequently, distribution of these peptides in the different kidney disease etiologies and normal kidney function was investigated via analysis of datasets recorded in the human proteome/peptidome database. All datasets, where eGFR was available and at least one of the complement peptides detected, were included. Results Twenty one different urinary peptides derived from complement could be identified. These peptide fragments originated from the complement factors C3, C4A and C4B, and CFB. Further investigation of 4557 datasets recorded in the urine proteome/peptidome database meeting the aforementioned inclusion requirements (eg available eGFR values and with at least one of the complement peptides detected), revealed, for most C3-derived peptides, an inverse, while for the majority of peptides derived from CFB, a positive association with eGFR. The table lists the detected complement derived peptides, the parental protein (Complement X), rho and p-value of the association with eGFR, and the number of samples (n) where the peptide was detected. When investigating the urine complement fragments, as a result of disease etiology, disease-specific distribution was detected, indicating a distinct association of complement factors and associated proteases, depending on disease etiology. As an example, the peptide distribution in AKI, IgA-Nephropathy (IgA-N) and vasculitis is shown in the Figure. Conclusion Multiple complement-derived peptides are significantly associated with kidney function, and with certain kidney disease etiologies, such as AKI, IgA-N or vasculitis. Proteomic screening of these complement factors may provide a basis, not only for non-invasively assessing kidney disease, but also for an opportunity to develop novel drugs; the latter, via targeting the associated proteases responsible for the release of these complement-derived peptides, in a specific kidney disease manner, in urine.

scholarly journals Associations between genetic risk variants for kidney diseases and kidney disease etiology

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Sebastian Wunnenburger ◽  
Ulla T. Schultheiss ◽  
Gerd Walz ◽  
Birgit Hausknecht ◽  
Arif B. Ekici ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Genetic Risk ◽  
Kidney Diseases ◽  
Disease Etiology ◽  
Risk Variants ◽  
Genetic Risk Variants

Stroke in chronic renal failure

2008 ◽  
Vol 149 (15) ◽  
pp. 691-696
Author(s):  
Dániel Bereczki
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Chronic Renal Disease ◽  
Kidney Diseases ◽  
Cerebrovascular Diseases ◽  
Lipid Lowering ◽  
Increased Risk ◽  
Intracerebral Hemorrhages

Chronic kidney diseases and cardiovascular diseases have several common risk factors like hypertension and diabetes. In chronic renal disease stroke risk is several times higher than in the average population. The combination of classical risk factors and those characteristic of chronic kidney disease might explain this increased risk. Among acute cerebrovascular diseases intracerebral hemorrhages are more frequent than in those with normal kidney function. The outcome of stroke is worse in chronic kidney disease. The treatment of stroke (thrombolysis, antiplatelet and anticoagulant treatment, statins, etc.) is an area of clinical research in this patient group. There are no reliable data on the application of thrombolysis in acute stroke in patients with chronic renal disease. Aspirin might be administered. Carefulness, individual considerations and lower doses might be appropriate when using other treatments. The condition of the kidney as well as other associated diseases should be considered during administration of antihypertensive and lipid lowering medications.

Ethnopharmacological Survey of Medicinal Plants Used in Traditional Treatment of Kidney Diseases in Fez–Meknes Region, Morocco

2019 ◽  
Vol 18 (2) ◽  
pp. 99-114
Author(s):  
M. Chebaibi ◽  
D. Bousta ◽  
I. Iken ◽  
H. Hoummani ◽  
A. Ech-Choayeby ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Medicinal Plants ◽  
Kidney Diseases ◽  
Rank Order ◽  
Pearson Correlation ◽  
Use Value ◽  
Traditional Treatment ◽  
Toxic Plants ◽  
A Value ◽  
Chi Squared

The purpose of this study was to inventory and collect information on plants and mixtures commonly used by herbalists to treat kidney disease in the Fez–Meknes region. We also aimed to compare the results obtained with the results of the other studies and exploit the correlations between different factors. An ethnopharmacological survey was conducted from 289 local herbalists in eight different areas of Fez–Meknes region. Ethnomedicinal uses and ethnobotanical indices were analyzed using quantitative tools, i.e., the total number of citation (TNC), use value (UV), family use value (FUV), fidelity level (FL), and rank order priority (ROP). Statistical analyses such as Pearson correlation and chi-squared test were performed to delineate any correlation. Two hundred and eighty-nine herbalists were questioned. Sixty-nine plant species belonging to 38 families were cited by herbalists for traditional treatment of kidney disease. The highest value of UV was obtained for Herniaria glabra L. (UV = 0.79), and Caryophyllaceae was the family frequently cited (FUV = 0.795). Ammodaucus leucotrichus Coss. & Dur. had the highest value of FL with a value of 100%, and the highest value of ROP was recorded for Herniaria glabra L. (ROP = 91%). Sociodemographic characteristics had a significant impact on the knowledge of toxic plants. Our study has revealed a cultural heritage linked to herbalism and a great wealth of medicinal plants, whose valorization and protection are necessary. Several studies are needed to sensitize herbalists and population on the danger of toxic plants, to extract chemical compounds from the main plants used, and to evaluate their toxicity.

scholarly journals Low Serum Uric Acid Predicts Risk of a Composite Disease Endpoint

Medicina ◽  
2021 ◽  
Vol 57 (4) ◽  
pp. 361
Author(s):  
Fatma Özpamuk-Karadeniz ◽  
Yusuf Karadeniz ◽  
Adnan Kaya ◽  
Servet Altay ◽  
Günay Can ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Density Lipoprotein ◽  
Positive Association ◽  
Composite Endpoint ◽  
Adverse Outcomes ◽  
Inverse Association ◽  
Adjusted Logistic Regression ◽  
Low Serum

Background and objectives: Mortality may increase in hypouricemia as well as inhyperuricemia. We assessed the predictive value of low serum uric acid (SUA) levels on the risk of overall mortality or a composite endpoint of death and nonfatal events. Materials and Methods: In 1013 community-based middle-aged adults, free of uncontrolled diabetes and coronary heart disease at baseline, the association of sex-specific SUA tertiles with defined outcomes was evaluated prospectively by logistic regression, stratified to gender and presence of type-2 diabetes, using recent criteria. Results: Totally, 43 deaths and additional incident nonfatal events in 157 cases were recorded at a median 3.4 years’ follow-up. Multivariable linear regression disclosed SUA to be significantly associated among non-diabetic individuals positively with creatinine, triglycerides, and body mass index in women further with fasted glucose. In multivariable-adjusted logistic regression analysis, sex-specifically dichotomized baseline uric acid (<5.1 and <4.1 mg/dL vs. higher values) significantly predicted the non-fatal events in the whole sample (relative risk (RR) 1.51 [95% confidence interval (CI) 1.02; 2.26]), as well as in men, while composite endpoint in the whole sample tended to rise (RR 1.38). Compared with the intermediate one, the top and bottom SUA tertiles combined tended to confer mortality risk (RR 2.40 [95% CI 0.89; 6.51]). Adverse outcomes in diabetic women were predicted by tertiles 2 and 3. Conclusions: Inverse association of SUA with adverse outcomes, especially in men, is consistent with the involvement of uric acid mass in autoimmune activation. The positive association of uric acid with adverse outcomes in diabetic women is likely mediated by concomitant high-density lipoprotein dysfunction.

scholarly journals Circulating miRNAs Related to Epithelial–Mesenchymal Transitions (EMT) as the New Molecular Markers in Endometriosis

2021 ◽  
Vol 43 (2) ◽  
pp. 900-916
Author(s):  
Anna Zubrzycka ◽  
Monika Migdalska-Sęk ◽  
Sławomir Jędrzejczyk ◽  
Ewa Brzeziańska-Lasota
Keyword(s):  
Molecular Mechanisms ◽  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
Clinical Symptoms ◽  
Diagnostic Tools ◽  
Endometrial Stromal Cells ◽  
Disease Etiology ◽  
Diagnostic Biomarkers ◽  
Mesenchymal Transition ◽  
Non Invasive

Endometriosis is a chronic gynecological disease defined by the presence of endometrial-like tissue found outside the uterus, most commonly in the peritoneal cavity. Endometriosis lesions are heterogenous but usually contain endometrial stromal cells and epithelial glands, immune cell infiltrates and are vascularized and innervated by nerves. The complex etiopathogenesis and heterogenity of the clinical symptoms, as well as the lack of a specific non-invasive diagnostic biomarkers, underline the need for more advanced diagnostic tools. Unfortunately, the contribution of environmental, hormonal and immunological factors in the disease etiology is insufficient, and the contribution of genetic/epigenetic factors is still fragmentary. Therefore, there is a need for more focused study on the molecular mechanisms of endometriosis and non-invasive diagnostic monitoring systems. MicroRNAs (miRNAs) demonstrate high stability and tissue specificity and play a significant role in modulating a range of molecular pathways, and hence may be suitable diagnostic biomarkers for the origin and development of endometriosis. Of these, the most frequently studied are those related to endometriosis, including those involved in epithelial–mesenchymal transition (EMT), whose expression is altered in plasma or endometriotic lesion biopsies; however, the results are ambiguous. Specific miRNAs expressed in endometriosis may serve as diagnostics markers with prognostic value, and they have been proposed as molecular targets for treatment. The aim of this review is to present selected miRNAs associated with EMT known to have experimentally confirmed significance, and discuss their utility as biomarkers in endometriosis.

scholarly journals CD73 Overexpression in Podocytes: A Novel Marker of Podocyte Injury in Human Kidney Disease

2021 ◽  
Vol 22 (14) ◽  
pp. 7642
Author(s):  
Zoran V. Popovic ◽  
Felix Bestvater ◽  
Damir Krunic ◽  
Bernhard K. Krämer ◽  
Raoul Bergner ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Membranous Glomerulonephritis ◽  
Human Kidney ◽  
Protective Role ◽  
Control Group ◽  
Podocyte Injury ◽  
Ccr2 Expression ◽  
Cd73 Expression

The CD73 pathway is an important anti-inflammatory mechanism in various disease settings. Observations in mouse models suggested that CD73 might have a protective role in kidney damage; however, no direct evidence of its role in human kidney disease has been described to date. Here, we hypothesized that podocyte injury in human kidney diseases alters CD73 expression that may facilitate the diagnosis of podocytopathies. We assessed the expression of CD73 and one of its functionally important targets, the C-C chemokine receptor type 2 (CCR2), in podocytes from kidney biopsies of 39 patients with podocytopathy (including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous glomerulonephritis (MGN) and amyloidosis) and a control group. Podocyte CD73 expression in each of the disease groups was significantly increased in comparison to controls (p < 0.001–p < 0.0001). Moreover, there was a marked negative correlation between CD73 and CCR2 expression, as confirmed by immunohistochemistry and immunofluorescence (Pearson r = −0.5068, p = 0.0031; Pearson r = −0.4705, p = 0.0313, respectively), thus suggesting a protective role of CD73 in kidney injury. Finally, we identify CD73 as a novel potential diagnostic marker of human podocytopathies, particularly of MCD that has been notorious for the lack of pathological features recognizable by light microscopy and immunohistochemistry.

scholarly journals The Mitochondrial Kinase PINK1 in Diabetic Kidney Disease

2021 ◽  
Vol 22 (4) ◽  
pp. 1525
Author(s):  
Chunling Huang ◽  
Ji Bian ◽  
Qinghua Cao ◽  
Xin-Ming Chen ◽  
Carol A. Pollock
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Kidney Diseases ◽  
Mitochondrial Protein ◽  
Physiological Role ◽  
Close Link ◽  
Promising Alternative ◽  
Diabetic Kidney ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog

Mitochondria are critical organelles that play a key role in cellular metabolism, survival, and homeostasis. Mitochondrial dysfunction has been implicated in the pathogenesis of diabetic kidney disease. The function of mitochondria is critically regulated by several mitochondrial protein kinases, including the phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1). The focus of PINK1 research has been centered on neuronal diseases. Recent studies have revealed a close link between PINK1 and many other diseases including kidney diseases. This review will provide a concise summary of PINK1 and its regulation of mitochondrial function in health and disease. The physiological role of PINK1 in the major cells involved in diabetic kidney disease including proximal tubular cells and podocytes will also be summarized. Collectively, these studies suggested that targeting PINK1 may offer a promising alternative for the treatment of diabetic kidney disease.

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