Exploring the relations of NLR, hsCRP and MCP-1 with type 2 diabetic kidney disease: a cross-sectional study.

Type 2 diabetic kidney disease (T2DKD) is a common microvascular complication of type 2 diabetes mellitus (T2DM), and its incidence is significantly increasing. Microinflammation plays an important role in the development of T2DKD. Based on this, this study investigated the value of inflammatory markers including neutrophil-lymphocyte ratio (NLR), high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1) in the prediction of T2DKD. This was a cross-sectional survey study. A total of 90 patients with T2DM, who were hospitalized in the nephrology and endocrinology departments of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from June 2021 to January 2022, were included and divided into three groups (A1, A2, A3) according to the urinary albumin-to-creatinine ratio (UACR). Observe and compare the basic information, clinical and laboratory data, and the inflammatory markers NLR, hs-CRP, MCP-1. Results revealed that high levels of NLR (OR = 6.562, 95% CI 2.060-20.902, P = 0.001) and MCP-1 (OR = 1.060, 95% CI 1.026-1.095, P < 0.001) were risk factors in the development of T2DKD. Receiver operating characteristic curve analysis showed that the area under curve of NLR and MCP-1 in diagnosing T2DKD were 0.760 (95% CI 0.6577-0.863, P < 0.001) and 0.862 (95% CI 0.7787-0.937, P < 0.001). Therefore, the inflammatory markers NLR and MCP-1 are risk factors affecting the development of T2DKD, which of clinical value may be used as novel markers of T2DKD.

Urinary MCP-1、HMGB1 increased in calcium nephrolithiasis patients and the influence of hypercalciuria on the production of the two cytokines.

The study aims to observe the urinary excretion of monocyte chemoattractant-1 (MCP-1) and high-mobility group box 1 (HMGB1) in patients with calcium nephrolithiasis and to determine the influence of hypercalciuria on the production of the two cytokines. 81 cases of patients with calcium nephrolithiasis (group CN) and 30 healthy controls (group C) were involved in this study. To observe the influence of urinary calcium on the excretion of those cytokines, the patients were subdivided according to their 24-h urinary calcium level: ≥4 mg/kg/day (group H) and <4 mg/kg/day (group N). MCP-1 and HMGB1 in urina sanguinis were determined for all subjects. In addition, in vitro study was done to determine the production of the two cytokines and index of apoptosis and oxidative injuries in human kidney epithelial cells (HK-2) exposed to three high levels of calcium. Data showed that both urinary MCP-1 and HMGB1 in group CN were higher than that of group C. When the patients were subdivided, comparisons among the three groups showed that both MCP-1 and HMGB1 in group H and group N were higher than group C, but there was no significant statistical difference between the two stone groups. In vitro study, the apoptosis rate of cells, the lactate dehydrogenase activities, the hydrogen peroxide, and 8-isoprostane concentrations in the medium all increased in accordance with the increased concentration of calcium supplemented. Compared with the control, mRNA expressions of MCP-1 and HMGB1 in cells and the protein concentrations of the two cytokines in the medium of calcium-supplemented groups increased significantly. Results showed that urinary MCP-1 and HMGB1 increased in calcium nephrolithiasis patients and hypercalciuria might affect the identical pathways (through the reactive oxygen species) with other factors in stimulating the production of MCP-1 and HMGB1 in vivo.

Pentosan polysulfate preserves renal microvascular P2X1 receptor reactivity and autoregulatory behavior in DOCA-salt hypertensive rats.

Inflammation contributes to ANG II-associated impairment of renal autoregulation and microvascular P2X1 receptor signaling, but its role in renal autoregulation in mineralocorticoid-induced hypertension is unknown. Autoregulatory behavior was assessed using the blood-perfused juxtamedullary nephron preparation. Hypertension was induced in uninephrectomized control rats (UNx) by subcutaneous implantation of a DOCA pellet plus administration of 1% NaCl in the drinking water (DOCA-salt) for 3 wk. DOCA-salt rats developed hypertension that was unaltered by anti-inflammatory treatment with pentosan polysulfate (DOCA-salt+PPS) but was suppressed with "triple therapy" (hydrochlorothiazide, hydralazine, and reserpine; DOCA-salt+TTx). Baseline arteriolar diameters were similar across all groups. UNx rats exhibited pressure-dependent vasoconstriction with diameters declining to 69 ± 2% of control at 170 mmHg, indicating intact autoregulation. DOCA-salt treatment significantly blunted this pressure-mediated vasoconstriction. Diameters remained between 91 ± 4 and 98 ± 3% of control over 65-170 mmHg, indicating impaired autoregulation. In contrast, pressure-mediated vasoconstriction was preserved in DOCA-salt+PPS and DOCA-salt+TTx rats, reaching 77 ± 7 and 75 ± 3% of control at 170 mmHg, respectively. ATP is required for autoregulation via P2X1 receptor activation. ATP- and ß,γ-methylene ATP (P2X1 receptor agonist)-mediated vasoconstriction were markedly attenuated in DOCA-salt rats compared with UNx (P < 0.05), but significantly improved by PPS or TTx (P < 0.05 vs. DOCA-salt) treatment. Arteriolar responses to adenosine and UTP (P2Y2 receptor agonist) were unaffected by DOCA-salt treatment. PPS and TTx significantly reduced MCP-1 and protein excretion in DOCA-salt rats. These results support the hypothesis that hypertension triggers inflammatory cascades but anti-inflammatory treatment preserves renal autoregulation in DOCA-salt rats, most likely by normalizing renal microvascular reactivity to P2X1 receptor activation.

Evaluation of cadmium-induced nephrotoxicity using urinary metabolomic profiles in sprague-dawley male rats.

The aim of this study was to investigate urinary metabolomic profiles associated with cadmium (Cd)-induced nephrotoxicity and their potential mechanisms. Metabolomic profiles were measured by high-resolution (1)H-nuclear magnetic resonance (NMR) spectroscopy in the urine of rats after oral exposure to CdCl2 (1, 5, or 25 mg/kg) for 6 wk. The spectral data were further analyzed by a multivariate analysis to identify specific urinary metabolites. Urinary excretion levels of protein biomarkers were also measured and CdCl2 accumulated dose-dependently in the kidney. High-dose (25 mg/kg) CdCl2 exposure significantly increased serum blood urea nitrogen (BUN), but serum creatinine (sCr) levels were unchanged. High-dose CdCl2 (25 mg/kg) exposure also significantly elevated protein-based urinary biomarkers including osteopontin, monocyte chemoattractant protein-1 (MCP-1), kidney injury molecules-1 (Kim-1), and selenium-binding protein 1 (SBP1) in rat urine. Under these conditions, six urinary metabolites (citrate, serine, 3-hydroxyisovalerate, 4-hydroxyphenyllactate, dimethylamine, and betaine) were involved in mitochondrial energy metabolism. In addition, a few number of amino acids such as glycine, glutamate, tyrosine, proline, or phenylalanine and carbohydrate (glucose) were altered in urine after CdCl2 exposure. In particular, the metabolites involved in the glutathione biosynthesis pathway, including cysteine, serine, methionine, and glutamate, were markedly decreased compared to the control. Thus, these metabolites are potential biomarkers for detection of Cd-induced nephrotoxicity. Our results further indicate that redox metabolomics pathways may be associated with Cd-mediated chronic kidney injury. These findings provide a biochemical pathway for better understanding of cellular mechanism underlying Cd-induced renal injury in humans.

Brazilian embauba (Cecropia pachystachya) extract reduces renal lesions in 5/6 nephrectomized rats.

INTRODUCTION: Cecropia pachystachya (CP) is a plant rich in polyphenols which inhibits the angiotensin-converting enzyme (ACE) in vitro. Angiotensin II (AII) has an important role in the renal lesion provoked by 5/6 nephrectomy (NE). This study evaluated the CP extract effect on renal lesions provoked by 5/6 NE. MATERIALS AND METHODS: Male Wistar rats submitted to 5/6 NE were treated or not treated with CP extract and followed for 90 days. Systemic blood pressure (SBP), albuminuria, renal functional and structural parameters, ACE activity, urinary levels of monocyte chemoattrant protein-1 (MCP-1) and transforming growth factor ß (TGF-ß) were evaluated. RESULTS: Albuminuria and hypertension were less intense in the treated (NE+CP) group compared to the untreated (NE) group. CP extract treatment reduced the fall in glomerular filtration rate observed in NE rats. Glomerulosclerosis, tubulointerstitial lesions, increase of macrophages and AII positive cells in the renal cortex, as well as increases in renal ACE activity, urinary levels of MCP-1 and TGF-ß were attenuated in NE rats by CP treatment. CONCLUSIONS: The treatment with CP extract reduced the SBP and functional and structural renal changes in 5/6 NE rats. These effects were associated with decreased AII expression, ACE activity and inflammation in the renal cortex.

Podocyte as a potential target of inflammation: role of pioglitazone hydrochloride in patients with type 2 diabetes.

OBJECTIVE: To observe the effects of pioglitazone hydrochloride on urinary sediment podocalyxin and monocyte chemoattractant protein-1 (MCP-1) excretion in patients with type 2 diabetes and to explore its possible renoprotective mechanisms. METHODS: Ninety-eight patients with uncontrolled type 2 diabetes, who were previously prescribed metformin, acarbose, or both, were randomly assigned to a DP group (add-on pioglitazone; n = 49) or a DS group (add-on sulfonylurea; n = 49). RESULTS: After 12 weeks of treatment, both add-on pioglitazone therapy (the DP group) and add-on sulfonylurea therapy (the DS group) demonstrated a similar improvement in fasting blood glucose and hemoglobin A1c, but systolic and diastolic blood pressure declined significantly in only the DP group. Moreover, the DP group showed significantly better efficacy in reducing urinary MCP-1 excretion in comparison with the DS group. Furthermore, both urinary albumin and urinary sediment podocalyxin excretion decreased significantly in the DP group but not in the DS group. The urinary sediment podocalyxin to creatinine ratio had a positive correlation with urinary albumin to creatinine ratio (r = 0.624; P<.01) and urinary MCP-1 to creatinine ratio (r = 0.346; P<.01). CONCLUSION: Pioglitazone treatment revealed a podocyte-protective capacity in patients with type 2 diabetes, and the underlying mechanisms may be partly attributed to its effective suppression of excessive local renal inflammation.

[Effects of bushen huoxue recipe on urinary levels of albumin, IL-6, TGF-beta1 and MCP-1 in chronic nephritis patients of shen-deficiency blood-stasis syndrome].

OBJECTIVE: To observe the effect of Bushen Huoxue Recipe (BSHXR, a Chinese medicine recipe for Shen reinforcing and blood circulation activating) on the levels of urinary albumin, interleukin-6 (IL-6), transforming growth factor-beta1 (TGF-beta1), and monocyte chemotactic protein-1 (MCP-1) in chronic nephritis patients of Shen-deficiency blood-stasis syndrome. METHODS: Forty-five patients were blocking assigned randomly to two groups, fifteen patients in the control group and thirty in the treatment group. All orally took Monopril 10 mg, once daily. But BSHXR was given additionally to patients in the treatment group after decocting,one dose per day (taken in two times). The treatment course for both groups was eight weeks. Besides, a normal control group consisting of six healthy subjects from health examination of Shuguang Hospital was set up. The 24-h urinary albumin and contents of TGF-beta1, IL-6 and MCP-1 in urine of all subjects were observed. RESULTS: Compared with before treatment the 24-h urinary albumin was obviously reduced in the treatment group, showing significant difference (P<0.01). The urinary 24-h albumin decreased in the control group, with statistical significance (P<0.05). Statistical difference existed between the treatment group and the control group after treatment (P<0.01). Compared with before treatment, urinary levels of IL-6, TGF-beta1, and MCP-1 were all down-regulated in the treatment group and the control group after treatment (P<0.01), and the decreasing of IL-6 and TGF-beta1, levels was more significant in the treatment group statistically (P<0.05). CONCLUSIONS: BSHXR could attenuate the albuminuria in patients of chronic nephritis. Its mechanism might be possibly correlated with its down-regulation of IL-6, TGF-beta1, and MCP-1 levels.

[Effect of triptolide on urinary monocyte chemottractant protein-1 in patients with diabetic nephropathy].

OBJECTIVE: To observe the change of urinary monocyte chemottractant protein-1 (MCP-1) in patients with diabetic nephropathy (DN), and to explore the therapeutic effect and mechanism of triptolide (TL) in treating DN. METHODS: Thirty-five patients in the treated group were treated with TL plus benazepril and thirty two patients in the control group were treated with benazepril alone for six months. The change of urinary MCP-1 was measured before and after treatment. RESULTS: Level of urinary MCP-1 in DN patients was significantly higher than that in healthy subjects (P < 0.01), but it could be significantly decreased after TL treatment, showing significant difference as compared with that in the control group (P < 0.05). CONCLUSION: Determination of urinary MCP-1 level is beneficial to know the degree of kidney inflammation in DN patients. TL can inhibit inflammatory reaction to decrease the level of urinary MCP-1, and thus improve the renal function.

Short-term effects of fish oil treatment on urinary excretion of high- and low-molecular weight proteins in patients with IgA nephropathy.

AIMS: Recently, it was shown that fish oil treatment improved renal survival in patients with IgA nephropathy. The precise mechanisms of this protective effect remained unclear. Omega-3 polyunsaturated fatty acids (PUFAs), important active substances of fish oil, are able to attenuate inflammatory responses. Thus, the renoprotective effects of fish oil may be the result of mitigation of glomerular or tubulo-interstitial inflammation. We hypothesized that such a decrease in glomerular or tubulo-interstitial inflammation could result in an improvement of glomerular permselectivity as reflected by the urinary excretion of IgG, or of tubular reabsorption capacity as reflected by the urinary excretion of low-molecular weight proteins (LMWPs), or a decrease of the excretion of the inflammatory mediators MCP-1 and TNF-alpha. METHODS: Twelve patients with a biopsy-proven IgA nephropathy, a persistent proteinuria of > 0.5 g/24 h, and an impairment of renal function (creatinine clearance 44 ml/min/1.73 m2, range 19-72) were treated with fish oil for 6 months. The daily dosage of PUFAs amounted to 3.0 g. Before start of treatment (month 0), at the end of treatment (month 6), and 6 months off treatment (month 12), renal measurements were carried out. Creatinine clearance (ECC) was measured after pretreatment with cimetidine. In timed urine samples albumin, IgG, the LMWPs beta2-microglobulin and alpha1-microglobulin, and both MCP-1 and TNF-alpha were measured. RESULTS: Six months of fish oil treatment had no effect on creatinine clearance (44 ml/min/1.73 m2 vs 42 ml/min/1.73 m2), the urinary excretion of albumin (1,594 +/- 284 vs 1,370 +/- 337 microg/min), IgG (84 +/- 16 vs 82 +/- 20 microg/min), beta2-microglobulin (medians: 1.0 vs 0.8 microg/min), alpha1-microglobulin (38 +/- 9 vs 53 +/- 15 microg/min), MCP-1 (medians: 720 vs 782 microg/min), or TNF-alpha (medians: 31 vs 27 microg/min). Mean arterial pressure gradually decreased from 102 +/- 4 to 96 +/- 4 mmHg at the end of the treatment (n.s.), however, the lowest value was observed after fish oil had been stopped for 6 months (93 +/- 3 mmHg, p < 0.05). Changes in the excretion of the urinary proteins during the 12-month study period were correlated to changes in blood pressure (r = 0.57, p < 0.01), independent of fish oil treatment. The course of the disease over the 12-month study period in our fish oil-treated patients was comparable to that of an untreated control group. CONCLUSIONS: Fish oil treatment in patients with IgA nephropathy, renal insufficiency and proteinuria did not affect the excretion of low- or high-molecular weight proteins, MCP-1 or TNF-alpha. Our data do not provide arguments for beneficial effects of fish oil treatment on glomerular permselectivity of tubulo-interstitial inflammation.