Natural products in attenuating renal inflammation via inhibiting the NLRP3 inflammasome in diabetic kidney disease.

Diabetic kidney disease (DKD) is a prevalent and severe complications of diabetes and serves as the primary cause of end-stage kidney disease (ESKD) globally. Increasing evidence indicates that renal inflammation is critical in the pathogenesis of DKD. The nucleotide - binding oligomerization domain (NOD) - like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most extensively researched inflammasome complex and is considered a crucial regulator in the pathogenesis of DKD. The activation of NLRP3 inflammasome is regulated by various signaling pathways, including NF- κB, thioredoxin-interacting protein (TXNIP), and non-coding RNAs (ncRNA), among others. Natural products are chemicals extracted from living organisms in nature, and they typically possess pharmacological and biological activities. They are invaluable sources for drug design and development. Research has demonstrated that many natural products can alleviate DKD by targeting the NLRP3 inflammasome. In this review, we highlight the role of the NLRP3 inflammasome in DKD, and the pathways by which natural products fight against DKD via inhibiting the NLRP3 inflammasome activation, so as to provide novel insights for the treatment of DKD.

An analysis of the etiologies and economic indexes of inpatients with stage 5 chronic kidney disease in North China.

Objective: The aim of this study was to analyze the epidemiological characteristics of the causes of chronic kidney disease (CKD) stage 5 patients in North China and to investigate the economic burden of those on hemodialysis (HD) or peritoneal dialysis (PD), as well as the associated influencing factors. Methods: General clinical information, etiological categories, and hospitalization costs for HD or PD were collected from 1,515 patients hospitalized with stage 5 CKD at the Affiliated Hospital of Hebei University from 2016 to 2018. Logistic regression analysis was used to analyze the independent influencing factors affecting patients' financial burden. Results: The highest rate of DN was found in patients aged 70 years or older (27.0%) and the highest incidence of primary glomerulopathy was found in patients aged <50 years (24.3%). Age, type of dialysis, and type of health insurance were independent influences on the total financial burden of patients, and the results of multifactorial logistic regression analysis showed that age [OR (95% CI): 1.009 (1.002, 1.020)] and type of dialysis [OR (95% CI): 1.746 (1.149, 2.659)] would increase the total financial burden. The type of health insurance would reduce the total financial burden [OR (95% CI): 0.222 (0.108, 0.418)]. Conclusion: Chronic kidney disease, with its complex etiology and the heavy financial burden required for treatment, remains a more serious public health problem globally, and it is therefore necessary to further improve medical coverage for dialysis patients, increase management efforts, broaden pro-poor policies and increase the accessibility of medical services in low- and middle-income areas.

GFR Estimation Using a Panel of Filtration Markers in Shanghai and Beijing.

RATIONALE & OBJECTIVES: Estimated glomerular filtration rate (eGFR) using creatinine and cystatin C (eGFRcr-cys) may be less accurate compared to measured GFR (mGFR) in China than in North America, Europe, and Australia due to variation across regions in their non-GFR determinants. The non-GFR determinants of ß2-microglobulin (B2M) and ß-trace protein (BTP) differ from those of creatinine and cystatin C. Thus, the average eGFR using all 4 markers (eGFRavg) could be more accurate than eGFRcr-cys in China. STUDY DESIGN: Diagnostic test study. SETTING & PARTICIPANTS: 1,066 participants in Shanghai and Beijing with creatinine and cystatin C and 666 participants with all 4 filtration markers. TESTS COMPARED: Index tests were previously developed equations for eGFR using creatinine, cystatin C, B2M, and BTP and combinations. The reference test was mGFR using plasma clearance of iohexol. We compared the performance of eGFRavg to eGFRcr-cys using the proportion of participants with errors in eGFR >30% of mGFR (1 - P30) and root mean square error (RMSE) of the regression of eGFR on mGFR on the logarithmic scale. We also compared classification and reclassification of mGFR categories using eGFRavg compared to eGFRcr-cys. OUTCOMES: Accuracy was significantly better for eGFRavg (1 - P30 of 10.4% and RMSE of 0.214) compared to eGFRcr-cys (1 - P30 of 13.8% and RMSE of 0.232; P = 0.004 and P = 0.006, respectively). However, improvements in accuracy did not generally translate into significant improvement in classification or reclassification of mGFR categories. LIMITATIONS: Study population may not be generalizable to clinical settings other than large urban medical centers in China. CONCLUSIONS: A panel of endogenous filtration markers including B2M and BTP in addition to creatinine and cystatin C may improve GFR estimation in China. Further study is necessary to determine whether GFR estimation using B2M and BTP can be improved and whether these improvements lead to useful clinical applications.

Aetiology of chronic kidney disease and risk factors for disease progression in Chinese subjects: A single-centre retrospective study in Beijing.

AIM: To assess the aetiological factors of chronic kidney disease (CKD) and factors associated with disease progression. METHODS: Single-centre retrospective study evaluating thorough electronic medical records of patients diagnosed with CKD at Peking University People's Hospital (April 2010-April 2015). The objectives were to identify the aetiological factors of CKD in Chinese patients and risk factors associated with CKD progression. RESULTS: Of 15 425 CKD patients, 12 380 had aetiology recorded. The leading aetiologies associated with CKD were chronic glomerulonephritis (CGN; 36.8%), hypertensive nephropathy (HTN; 28.5%) and diabetic nephropathy (DN; 27.1%). CGN was most common in patients with early stage disease (stages 1-2); DN and HTN were common in advanced-stages (stages 3-4). In a longitudinal subcohort of 2923 patients with ≥6-month follow-up, 19.6% experienced CKD progression. Patients with CKD progression were significantly older in age and had a greater number of comorbidities and laboratory anomalies, and were more likely to have DN (40.5%) and CGN (40.5%) than HTN (5.5%) at baseline than patients without progression. In a multivariate analysis, factors associated with disease progression included macro- and micro-albuminuria, anaemia, hyperkalaemia, hyperphosphataemia, metabolic acidosis, CKD stage 4 and type 2 diabetes mellitus (T2DM). CONCLUSION: This study identified CGN, DN and HTN as the leading aetiological factors for CKD in Chinese patients. DN was a strong predictor of faster disease progression, with albuminuria (a complication of T2DM) associated with highest risk for disease progression.

Statin therapy and erythropoiesis-stimulating agent hyporesponsiveness in patients with nondialysis chronic kidney disease: A retrospective study in Beijing, China.

Erythropoiesis-stimulating agents (ESAs) are frequently used among patients with renal anemia, while a significant proportion of patients exhibit ESA hyporesponsiveness despite adequate dosing. Previous studies have suggested an inverse association between ESA hyporesponsiveness and statin use among patients receiving dialysis therapy. However, studies based on predialysis patients are extremely limited.Based on electronic medical records of a tertiary hospital in Beijing, China between April 2010 and April 2015, we investigated the association between statin use and ESA hyporesponsiveness among patients with predialysis-chronic kidney disease (CKD).Altogether 232 patients with CKD initiating ESA therapy and with hemoglobin levels monitored for at least 6 months were included in our analyses. Among them, 77 (38.5%) were long-term statin users (regular statin treatment for more than 3 months) before ESA initiation. Overall, 6.5% of the statin users and 17.1% of nonusers were considered to have ESA hyporesponsiveness. Long-term statin therapy was significantly associated with a lower proportion of ESA hyporesponsiveness in fully adjusted model (odds ratio 0.15, 95% confidence interval: 0.03-0.64).We found that long-term statin therapy was inversely associated with ESA hyporesponsiveness among predialysis patients with CKD. Further studies are needed to validate our observations, and to explore the potential mechanisms between ESA resistance and statin therapy.

Accuracy of iohexol plasma clearance for GFR-determination: a comparison between single and dual sampling.

BACKGROUND: Current guidelines regarding plasma-sampling techniques for glomerular filtration rate (GFR) determination are inconsistent. Single-sample methods are commonly believed not to be precise enough to meet clinical demands. The present study compared the agreement between single- and dual- plasma sampling methods with a three-point plasma clearance of iohexol. METHODS: A total of 46 healthy volunteers and 124 chronic kidney disease (CKD) patients with varying degrees of renal dysfunction received 5 ml iohexol (300 mgI/ml) i.v. and plasma samples were drawn at 2-, 3- and 4-h post-injection. Plasma-iodine concentrations were detected by high-performance liquid chromatography (HPLC). RESULTS: Bias was similar among single-plasma sampling methods (SPSM) and dual-plasma sampling methods (DPSM). The best correlation was obtained from the 2- and 4-h DPSM (concordance correlation coefficient [CCC]: 0.9988) with none of the estimates differed by more than 30% from the reference GFR and only one (0.06%) estimate differed by more than 10% (P30, 100%; P10, 99.4%). SPSM using samples around 3- or 4-h demonstrated acceptable accuracy at a GFR level of ≥60 ml/min/1.73m2 (P30 = 100% and P10 > 75% for both measurements). CONCLUSION: 4-h SPSM is advantageous in clinical practice in subjects with GFR ≥ 60 ml/min/1.73m2. For patients with an expected GFR < 60 ml/min/1.73m2, a prolonged sampling time is more reliable.

A case report of POEMS syndrome with renal involvement as immunotactoid glomerulopathy.

RATIONALE: POEMS syndrome is a rare multi-system disorder, which sometimes involves the kidney. Immunotactoid glomerulopathy (ITG) is an uncommon glomerular disease resulted from deposits of immunoglobulins and its derivatives. ITG caused by POEMS syndrome is rarely reported. PATIENT CONCERNS: A 63-year-old man was presented with acute kidney injury. In addition, it's found that he had abnormal serum free κ /λ ratio, polyneuropathy, Castleman's disease, organomegaly, endocrinopathy and skin changes. DIAGNOSES: POEMS syndrome was diagnosed, Renal biopsy revealed an ITG. INTERVENTIONS: Dexamethasone and thalidomide were given, as well as hemodialysis and other supportive treatments. OUTCOMES: The patient's extrarenal manifestations improved gradually and his renal function also showed slight improvement. LESSONS: ITG caused by POEMS syndrome is rare, however, it makes sense that the monoclonal proteins produced by the plasma cells could cause ITG. Chemotherapy similar to that employed in multiple myeloma may be beneficial for these patients.