scholarly journals Chronic treatment with the (iso-)glutaminyl cyclase inhibitor PQ529 is a novel and effective approach for glomerulonephritis in chronic kidney disease

2020 ◽  
Author(s):  
Naotoshi Kanemitsu ◽  
Fumiko Kiyonaga ◽  
Kazuhiko Mizukami ◽  
Kyoichi Maeno ◽  
Takashi Nishikubo ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Repeated Administration ◽  
Urinary Protein ◽  
Kidney Cortex ◽  
Dependent Manner ◽  
Glutaminyl Cyclase ◽  
Protein Excretion ◽  
Urinary Protein Level ◽  
Wistar Kyoto

Abstract Glomeruli and renal tubule injury in chronic kidney disease (CKD) is reported to involve induction of macrophage activation through the CCL2/CCR2 axis. The effects of inhibitors of the CCL2/CCR2 axis, such as anti-CCL2 antibody and CCR2 antagonist, on kidney function in animal models or humans with kidney dysfunction have been demonstrated. The N-terminal glutamine on immature CCL2 is replaced with pyroglutamate (pE) by glutaminyl cyclase (QC) and isoQC. pE-CCL2 is stable and resistant to peptidases. We hypothesized that inhibiting QC/isoQC activity would lead to the degradation of CCL2, thereby ameliorating CKD and reducing kidney inflammation. To test this hypothesis, we investigated the renoprotective properties of the QC/isoQC inhibitor PQ529 in anti-glomerular basement membrane (GBM) antibody–induced glomerulonephritis Wistar Kyoto (WKY) rats. Three-week repeated administration of PQ529 (30 and 100 mg/kg, twice daily) significantly reduced the serum and urine CCL2 and urinary protein excretion in a dose-dependent manner. Correlations between the urinary protein level and serum or urinary CCL2 levels were confirmed in tested animals. Repeated administration of PQ529 significantly reduced the expression of CD68, a macrophage marker, in the kidney cortex and mononuclear infiltration into the tubulointerstitium. In addition, decreased levels of urinary KIM-1, β2 microglobulin, and clusterin were detected, suggesting the inhibition of inflammation in both the proximal and distal tubules. These results suggest that PQ529 suppresses the progression of inflammation-induced renal dysfunction by inhibiting the CCL2/CCR2 axis. Inhibition of QC/isoQC may thus be a viable alternative therapeutic approach for treating glomerulonephritis and CKD patients.

Beneficial effect of aliskiren combined with olmesartan in reducing urinary protein excretion in patients with chronic kidney disease

2011 ◽  
Vol 44 (3) ◽  
pp. 841-845 ◽  
Author(s):  
Takahito Moriyama ◽  
Yuki Tsuruta ◽  
Chiari Kojima ◽  
Mitsuyo Itabashi ◽  
Hidekazu Sugiura ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Beneficial Effect ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Protein Excretion

Effect of Spironolactone on Urinary Protein Excretion in Patients with Chronic Kidney Disease

Renal Failure ◽  
2009 ◽  
Vol 31 (10) ◽  
pp. 928-932 ◽  
Author(s):  
Erkan Sengul ◽  
Tayfun Sahin ◽  
Erce Sevin ◽  
Ahmet Yilmaz
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Protein Excretion

scholarly journals Soluble Fas affects erythropoiesis in vitro and acts as a potential predictor of erythropoiesis-stimulating agent therapy in patients with chronic kidney disease

2020 ◽  
Vol 318 (4) ◽  
pp. F861-F869
Author(s):  
Daniela Mendes Chiloff ◽  
Danilo Candido de Almeida ◽  
Maria A. Dalboni ◽  
Maria Eugênia Canziani ◽  
Sunil K. George ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Dependent Manner ◽  
Potential Predictor ◽  
Soluble Fas ◽  
Esa Therapy

Serum soluble Fas (sFas) levels are associated with erythropoietin (Epo) hyporesponsiveness in patients with chronic kidney disease (CKD). Whether sFas could predict the need for erythropoiesis-stimulating agent (ESA) usage and its influence in erythropoiesis remain unclear. We evaluated the relation between sFas and ESA therapy in patients with CKD with anemia and its effect on erythropoiesis in vitro. First, we performed a retrospective cohort study with 77 anemic patients with nondialysis CKD. We performed in vitro experiments to investigate whether sFas could interfere with the behavior of hematopoietic stem cells (HSCs). HSCs were isolated from umbilical cord blood and incubated with recombinant sFas protein in a dose-dependent manner. Serum sFas positively correlated with Epo levels ( r = 0.30, P = 0.001) but negatively with hemoglobin ( r = −0.55, P < 0.001) and glomerular filtration rate ( r = −0.58, P < 0.001) in patients with CKD at baseline. Elevated sFas serum levels (4,316 ± 897 vs. 2,776 ± 749, P < 0.001) with lower estimated glomerular filtration rate (26.2 ± 10.1 vs. 33.5 ± 14.3, P = 0.01) and reduced hemoglobin concentration (11.1 ± 0.9 vs. 12.5 ± 1.2, P < 0.001) were identified in patients who required ESA therapy compared with patients with non-ESA. Afterward, we detected that the sFas level was slight correlated with a necessity of ESA therapy in patients with nondialysis CKD and anemia. In vitro assays demonstrated that the erythroid progenitor cell frequency negatively correlated with sFas concentration ( r = −0.72, P < 0.001). There was decreased erythroid colony formation in vitro when CD34+ HSCs were incubated with a higher concentration of sFas protein (1.56 ± 0.29, 4.33 ± 0.53, P < 0.001). Our findings suggest that sFas is a potential predictor for ESA therapy in patients with nondialysis CKD and that elevated sFas could affect erythropoiesis in vitro.

scholarly journals P0949EFFECT OF DIETARY PHOSPHORUS RESTRICTION ON FIBROBLAST GROWTH FACTOR,KLOTHO AND BODY COMPOSITION IN CHRONIC KIDNEY DISEASE PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Trisha Sachan ◽  
Anita Saxena ◽  
Amit Gupta
Keyword(s):  
Chronic Kidney Disease ◽  
Body Composition ◽  
Renal Function ◽  
Kidney Disease ◽  
Urinary Protein ◽  
Dietary Phosphorus ◽  
Ckd Stage ◽  
Significant Difference ◽  
The Mean ◽  
Fgf 23

Abstract Background and Aims Changes in dietary phosphorus regulate serum FGF-23, parathyroid hormone, 1,25(OH)(2)D and Klotho concentrations . Cardiovascular disease (CVD) is the principal killer of patients with chronic kidney disease and hyperphosphetemia is a potent risk factor it. Of many causative factors for CVD in CKD, dietary interventions involving restriction of dietary phosphorous intake can help reduce onset of CVD at early stages of CKD with other corrective measures. Muscle wasting is a consequence of uremic syndrome which alters body composition. The aim of the study was to study effect of dietary phosphorous restriction on FGF-23, iPTH, Klotho, 1,25(OH)(2)D and body composition in chronic kidney disease patients. Method This is a longitudinal study with 12 months intervention, approved by Ethics Committee of the institute. A total 132 subjects were recruited (66 healthy controls, 66 CKD patient. of 66 patients 33 were in CKD stage 1 and 33 in stage 2. GFR was calculated with the help of MDRD formula. Biochemical parameters of subjects were evaluated at baseline, 6 and 12 months along with the anthropometric measurements (body weight, height, mid upper arm circumference (MUAC), and skin folds). Three days dietary recall was taken to evaluate energy, protein and phosphorous intake. CKD patients whose dietary phosphorous intake was more than 1000 mg/day, were given intense dietary counseling and prescribed dietary modifications by restricting dietary phosphorous between 800-1000 mg/day. Results The mean age of controls and patients was 37.01±9.62 and 38.27±12.06 and eGFR of 136.94±11.77 and 83.69±17.37 respectively. One way ANOVA showed significant difference among controls and the study groups in hemoglobin (p&lt;0.001), s albumin (p&lt;0.001), FGF-23 (p&lt;0.001), klotho (p&lt;0.001), urinary protein (p&lt;0.001) and Nephron Index (p&lt;0.001).The mean energy intake (p = 0.001) and dietary phosphorous intake (p&lt;0.001) of the CKD patients decreased significantly with the decline in the renal function along with the anthropometric measures i.e. BMI (p = 0.041),WHR (p = 0.015) and all four skin folds (p&lt;0.001). On applying Pearson’s correlation, eGFR correlated negatively with urinary protein (-0.739, 0.000), FGF-23 (-0.679, 0.000) and serum phosphorous (-0.697, 0.000) and positively with klotho (0.872, 0.000). FGF-23 correlated negatively with klotho (-0.742, 0.000). Dietary phosphorous was found to be positively correlated with urinary protein (0.496, 0.000), serum phosphorous (0.680, 0.000) and FGF-23 (0.573, 0.000) and negatively with Klotho (-0.602, 0.000). Nephron index revealed a positive correlation with eGFR (0.529, 0.000). Urinary protein correlated negatively with klotho (-0.810, 0.000). A multiple linear regression was run to predict eGFR from anthropometric variables such as BMI, WHR, MUAC, skin folds thickness and handgrip strength. All anthropometric variables predicted decline in eGFR (p&lt;0.05, R2 =0.223). At 6 and 12 months; repeated ANOVAs analysis showed a statistically significant difference in serum creatinine (p=0.000), serum phosphorous (p=0.000), FGF-23(p=0.000) and klotho (p=0.000). Conclusion Elevated levels of FGF-23 and decreased Klotho levels, with the moderate decline in renal function improved with the restricted phosphorous diet at 6 and 12 months emphasizing the importance of phosphorus restriction at an early stage.

Proteinuria

2020 ◽  
Vol 13 (3) ◽  
pp. 152-158
Author(s):  
Lauren Copeland ◽  
Keith Gillis
Keyword(s):  
Primary Care ◽  
Chronic Kidney Disease ◽  
Risk Factor ◽  
Kidney Disease ◽  
Early Detection ◽  
Renal Disease ◽  
Independent Risk Factor ◽  
Prognostic Significance ◽  
Urinary Protein ◽  
Progression Of Renal Disease

Measurement of urinary protein is an essential part of the evaluation of chronic kidney disease; it has both diagnostic and prognostic significance. Proteinuria is an independent risk factor for progression of renal disease, but is also independently associated with increased cardiovascular mortality. Despite its far-reaching implications, the definition, diagnosis and treatment of proteinuria can cause confusion in primary care. Early detection of proteinuria in the context of diabetes or otherwise is vital given the potential for intervention to reduce urinary protein losses and improve renal and cardiovascular outcomes. This article will focus on the definition, potential causes and management of proteinuria, including which individuals should be referred to secondary care.

scholarly journals P0768NOVEL URINARY PROTEIN BIOMARKERS FOR UROTHELIAL CANCER IN PATIENTS WITH CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Chiu-Ching Huang ◽  
Che-Yi Chou ◽  
Kuo-Hsiung Shu ◽  
Hung-Chun Chen ◽  
Ming-Chang Wang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Urothelial Cancer ◽  
Structured Interview ◽  
Urinary Protein ◽  
Screening Tools ◽  
Large Sample Size ◽  
Healthy Controls ◽  
Protein Biomarkers ◽  
Biomarker Panel

Abstract Background and Aims Introduction: Chronic kidney disease (CKD) patients are known to have greater risk of urothelial cancer (UC) than general population. Urine is the most non-invasive examination and is directly linked to UC. Urinalysis and urine cytology are the major screening tools; however, these tests have low sensitivity or specificity in early disease. In this study, we used both normal and Non-UC CKD patients as controls to discover novel and more specific protein biomarkers in urine for early UC diagnosis. Aims To discover novel and more specific urinary protein biomarkers for screening of urothelial cancer (UC) in CKD patients. Method This is a multicenter prospective cohort study, carried out at 10 nationwide hospitals covering different regions of Taiwan from 2013-2018. Subjects were Taiwanese healthy adults (healthy controls, n=210), patients with CKD but without UC (disease controls, n=273) and patients with ongoing UC (n=211). For non-UC patients, urine and blood specimens were collected at the time of the structured interview. For UC patients, urine and blood samples were collected before operation. iTRAQ-LC-MS/MS approach was applied to compare protein expression among normal, CKD and UC cohorts. Results A total of 3838 proteins in urine were identified and 2497 proteins of them can be quantified. By filtering with fold changes, published papers and Human ATLAS, 27 candidates were selected as potential biomarkers and were validated with ELISA assay in a large sample size of urine specimens. Among the 27 candidates, we found BRDT, CYBP, GARS and HDGF were highly-expressed in the UC cohort when compared to normal and CKD cohorts (Figure 1). To increase the diagnostic value of UC, we combined ROC of our newly discovered 4 protein biomarkers. The AUC values of our newly discovered 4-biomarker panel were higher than the AUC values of the published biomarker panel, including the FDA-approved protein biomarkers (Figure 2). Conclusion We discover and validate a highly specific urinary protein biomarker panel (BRDT, GARS, HDGF and CYBP) to distinguish UC from CKD and healthy controls. It may be used for high throughput screening of subjects, such as CKD patients, who are at high risk to develop UC.

Proteinuria in health and disease assessed by measuring the urinary protein/creatinine ratio.

1987 ◽  
Vol 33 (2) ◽  
pp. 297-299 ◽  
Author(s):  
J Lemann ◽  
B T Doumas
Keyword(s):  
Kidney Disease ◽  
Urinary Protein ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Protein Excretion ◽  
Daily Excretion ◽  
Normal Mean ◽  
Health And Disease ◽  
Tract Disease ◽  
Excretion Rates

Abstract We measured daily excretion rates for urinary protein and the ratios of urinary protein to creatinine in 24-h urines and in untimed urines in 60 healthy adults, 30 patients with kidney disease, and 22 kidney-transplant recipients. The ratios for urinary protein/creatinine, mg/g, in untimed urines and in 24-h urines from the same subjects were closely correlated (r = 0.97) for rates of protein excretion ranging from normal (mean 44 mg/day) to nephrotic (maximum 19,300 mg/day). Because urinary protein/creatinine in healthy subjects never exceeded 100 mg/g, we propose that a ratio of less than 100 mg/g in untimed urines, obtained in the absence of exercise, fever, or other evidence of urinary tract disease, is a criterion of normal kidney function. Among patients with nephrotic syndrome (urinary protein excretion rate greater than or equal to 4000 mg/day), urinary protein/creatinine ratios always exceeded 2000 mg/g in both 24-h and untimed urines. Intermediate urinary protein/creatinine ratios (100 to 2000 mg/g) may reflect any type of kidney disease.

Vitamin K Metabolism in a Rat Model of Chronic Kidney Disease

2016 ◽  
Vol 45 (1) ◽  
pp. 4-13 ◽  
Author(s):  
Kristin M. McCabe ◽  
Sarah L. Booth ◽  
Xueyan Fu ◽  
Emilie Ward ◽  
Michael A. Adams ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vitamin K ◽  
Rat Model ◽  
Relative Increase ◽  
Kidney Cortex ◽  
Vitamin K Deficiency ◽  
Tissue Concentrations ◽  
K Deficiency ◽  
Very High

Background: Patients with chronic kidney disease (CKD) have very high levels of uncarboxylated, inactive, extra-hepatic vitamin K-dependent proteins measured in circulation, putting them at risk for complications of vitamin K deficiency. The major form of vitamin K found in the liver is phylloquinone (K1). Menaquinone-4 (MK-4) is the form of vitamin K that is preferentially found in extra-hepatic tissues. Methods: In the present study, we assessed tissue concentrations of K1 and MK-4 and the expression of vitamin K-related genes in a rat model of adenine-induced CKD. Results: It was found that rats with both mild and severe CKD had significantly lower amounts of K1 measured in liver, spleen and heart and higher levels of MK-4 measured in kidney cortex and medulla. All animals treated with high dietary K1 had an increase in tissue levels of both K1 and MK-4; however, the relative increase in K1 differed suggesting that the conversion of K1 to MK-4 may be a regulated/limiting process in some tissues. There was a decrease in the thoracic aorta expression of vitamin K recycling (Vkor) and utilization (Ggcx) enzymes, and a decrease in the kidney level of vitamin K1 to MK-4 bioconversion enzyme Ubiad1 in CKD. Conclusion: Taken together, these findings suggest that CKD impacts vitamin K metabolism, and this occurs early in the disease course. Our findings that vitamin K metabolism is altered in the presence of CKD provides further support that sub-clinical vitamin K deficiency may represent a modifiable risk factor for vascular and bone health in this population.

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