Use of low-protein staple foods in the dietary management of patients with stage 3-4 chronic kidney disease: a prospective case-crossover study.

OBJECTIVE: Maintaining a low-protein diet (LPD) is important for patients with chronic kidney disease (CKD) to delay renal degradation and alleviate clinical symptoms. For most patients with CKD, it is difficult to maintain the necessary low level of dietary protein intake (DPI). To improve the current dietary management of CKD, we conducted an intervention study by administering low-protein staple foods (LPSF). DESIGN AND METHODS: We conducted a prospective case-crossover study among 25 patients with stage 3-4 CKD. During the initial 12 weeks of the study, we instructed the patients regarding a standard LPD according to the recommendations of a renal dietitian. In the second stage of the study, we requested the patients taking low-protein rice or low-protein flour (250 g/d) as an LPSF diet instead of regular staple food daily, and followed these patients up for 12 weeks. We compared the DPI, dietary energy intake (DEI), normalized protein equivalent of total nitrogen appearance (nPNA), serum creatinine levels, and nutritional index between baseline and the end of the study. RESULTS: We found no change in dietary variables among the patients during the first 12 weeks of the LPD. After subjecting them to an LPSF diet, the corresponding variables showed a pronounced change. The patients' DPI decreased from 0.88 ± 0.20 to 0.68 ± 0.14 g/kg/d (P < 0.01) and the nPNA value decreased from 0.99 ± 0.18 to 0.87 ± 0.19 g/kg/d (P < 0.01). The high biological value protein intake proportion increased from 42% (baseline) to 57% (P < 0.01) during the 24 weeks. No variation was found in the measured DEI (28.0 ± 5.8 vs 28.6 ± 5.4 kcal/kg/d), nutrition assessment, or renal function and serum creatinine levels. CONCLUSION: Our prospective case-crossover study demonstrated that an LPSF diet can help patients with stage 3-4 CKD reduce DPI and nPNA values, improve the proportion of highly bioavailable proteins, ensure adequate calorie intake, and avoid malnutrition. An LPSF diet is an effective and simple therapy for patients with stage 3-4 CKD.

Serum fatty acid binding protein 4 levels are associated with abdominal aortic calcification in peritoneal dialysis patients.

BACKGROUND: Fatty acid binding protein 4 (FABP4) is an adipokine that was mainly derived from adipocytes and macrophages. Vascular calcification (VC) is highly prevalent in peritoneal dialysis (PD) patients and could predict their cardiovascular mortality. The pathogenesis of VC is complex, and adipokines may play an important role in it. This study aimed to examine the relationship between serum FABP4 and VC in PD patients. METHODS: Serum FABP4 was measured by enzyme-linked immunosorbent assay. According to the median value of serum FABP4, the participants were divided into the low FABP4 group and the high FABP4 group. Lateral plain X-ray films of abdomen were used to evaluate the abdominal aortic calcification (AAC) score. The participants were divided into the high AAC score group (AAC score ≥4, indicating moderate or heavy VC) and the low AAC score group (AAC score <4, indicating no or mild VC). RESULTS: 116 PD patients were involved in the study. The AAC score and the proportion of patients with an AAC score ≥4 of the high FABP4 group were significantly higher than those of the low FABP4 group. Serum FABP4 of the high AAC score group was significantly higher than that of the low AAC score group [164.5 (138.4, 362.8) ng/mL versus 144.7 (123.8, 170.1) ng/mL, p = 0.002]. Serum FABP4 was positively associated with the AAC score according to the multivariate linear regression analysis. In the multivariate logistic regression analysis, serum FABP4 was the independent influencer of an AAC score ≥4. CONCLUSIONS: Serum FABP4 is positively associated with the AAC score and is an independent marker of AAC in PD patients.

Upregulation of soluble epoxide hydrolase in proximal tubular cells mediated proteinuria-induced renal damage.

Epoxyeicosatrienoic acids, hydrolyzed by soluble epoxide hydrolase (sEH), have multiple biological functions, including the regulation of vascular tone, renal tubular transport, and being anti-inflammatory. Inhibitors of sEH have been demonstrated to be antihypertensive and renal protective. To elucidate the role of sEH in glomerulonephritis, we first determined the expression of sEH in human kidney by examining biopsies from 153 patients with a variety of glomerulonephritis, including minimal-change, membranous, and IgA nephropathy. Immunohistochemical staining of frozen kidney biopsy samples revealed sEH preferentially expressed in the renal proximal tubular cells, and its expression increased in all patients with glomerulonephritis. The level of sEH in the cortex was positively correlated with proteinuria and negatively with serum albumin level. To investigate the role of sEH in proteinuria-induced renal damage, we incubated purified urine protein from patients with rat renal proximal tubular epithelial cells in vitro. The level of sEH was elevated, as were monocyte chemoattractant protein 1 and the process of tubular epithelial-to-mesenchymal transition, characterized with increased α-smooth muscle actin (α-SMA) and decreased E-cadherin. These effects were attenuated by administration of a potent sEH inhibitor and mimicked with adenovirus-mediated sEH overexpression. In adriamycin-induced nephropathic mice, sEH inhibitor did not ameliorate proteinuria or level of serum albumin but reduced the long-term elevated serum creatinine level, interstitial inflammation, fibrosis, and α-SMA expression. Thus upregulation of sEH in proximal tubular cells in chronic proteinuric kidney diseases may mediate proteinuria-induced renal damage; sEH inhibition by increasing renal eicosanoid levels could prevent the progression of chronic proteinuric kidney diseases.

[Analysis of clinical state for arteriosclerosis obliterans in lower extremity of diabetic patients on peritoneal dialysis].

OBJECTIVE: To investigate the prevalence of arteriosclerosis obliterans in lower extremity and its influence factors in diabetic patients on peritoneal dialysis. METHOD: In this single center cross-sectional study, 74 with diabetic patients on peritoneal dialysis were recruited. The general information, dialysis program, laboratory examination and dialysis adequacy test results were recorded.Their symptoms and signs of arteriosclerosis obliterans in lower extremities were investigated and ankle brachial index (ABI) was determined. RESULT: In this study,70.3% of the patients had different degrees of symptoms and signs of arteriosclerosis obliterans in lower extremity. With Fortaine classification, 13.5% of the patients were in early lesions phase, 28.8% in local ischemic phase, 51.9% in nutritional disturbance phase, and 5.8% in gangrene phase. The patients were divided into three groups base on Fontaine classification: control group (no symptoms), mild group(early lesions phase and local ischemic phase) and severe group(nutritional disturbance phase and gangrene phase). There was a significant difference between the insulin dose, left foot ABI levels, plasma albumin levels and total Kt/V levels among the three groups (P<0.05). The plasma albumin levels and insulin doses were independent factors associated with arteriosclerosis obliterans in lower extremity (P<0.05). CONCLUSION: In diabetic patients on peritoneal dialysis, there is a high prevalence of arteriosclerosis obliterans in lower extremity, which is related to high insulin dosage and low serum albumin levels.

Association between serum cartilage oligomeric matrix protein and coronary artery calcification in maintenance hemodialysis patients.

BACKGROUND: Coronary artery calcification (CAC) is common in end-stage renal disease (ESRD) patients, and the extent of CAC is closely related to cardiovascular outcomes in ESRD patients. Cartilage oligomeric matrix protein (COMP), as a component of the vascular matrix, has been found to be an inhibitor of arterial calcification in basic studies. However, there is no clinical research on the correlation between COMP and CAC in maintenance hemodialysis (MHD) patients. The aim of this study was to explore the relationship between serum COMP levels and CAC and cardiovascular events in MHD patients. METHODS: Serum COMP levels were compared between 54 MHD patients and 66 healthy people. MHD patients were then divided into three groups according to the tertiles of the concentration of COMP level and were followed up for major adverse cardiac events (MACEs), which were defined as a combined end point of new onset angina pectoris, nonfatal myocardial infarction, heart failure, coronary artery revascularization, hospitalization due to angina pectoris and all-cause deaths. The CAC score was calculated based on computed tomography scans. RESULTS: The serum COMP level in MHD patients was significantly higher than that in the general population [984.23 (248.43-1902.61) ng/mL vs. 219.01 (97.26-821.92) ng/mL, P < 0.01]. Serum COMP levels were positively correlated with CAC (r = 0.313, P = 0.021) and serum parathyroid hormone in MHD patients (r = 0.359, P < 0.01). Linear regression suggested that after adjusting for age, fasting blood glucose (Glu) and glycosylated hemoglobin (HbAlc), CAC score was an independent predictor in the final model for COMP level (ß = 0.424, t = 3.130, P < 0.01). The receiver operating characteristic (ROC) curve showed that COMP ≥ 994 mg/mL had 68.0% sensitivity and 72.4% specificity for the prediction of severe CAC [area under the curve (AUC): 0.674, P = 0.030, 95% CI: 0.526-0.882]. After a median follow-up of 16 months (8-24 months), there was no difference in the incidence rate of MACEs between the upper, middle and lower serum COMP groups. CONCLUSIONS: Our study found that MHD patients have higher levels of circulating COMP than controls. The serum COMP level is positively correlated with CAC score and could be used as a biomarker of severe CAC in MHD patients. However, there is no obvious correlation between serum COMP levels and the incidence of cardiovascular events.

Retraction statement: 'Urotensin II inhibits autophagy in renal tubular epithelial cells and induces extracellular matrix production in early diabetic mice' by Guan­Jong Chen, Fei Wu, Xin­Xin Pang, Ai­Hua Zhang, Jun­Bao Shi, Min Lu and Chao­Shu Tang

AIMS/INTRODUCTION: Urotensin II (UII) and autophagy have been considered as important components in the pathogenesis of diabetic nephropathy. The present study explores whether UII can regulate autophagy in the kidney, and its effect in diabetes. MATERIALS AND METHODS: Immunohistochemistry and western blot were carried out on the kidney tissues of diabetic UII receptor (UT) gene knockout mice, wild-type diabetic mice and normal control mice. For the in vitro experiment, HK-2 cells were treated with UII (10-7 mol/L) in the presence or absence of UT antagonist, SB-657510, (10-6 mol/L) or autophagy inducer, rapamycin (10-3 mol/L), for 12 h. Markers for autophagy (LC3-II, p62/SQSTM1) and extracellular matrix (fibronectin, collagen IV) were analyzed. RESULTS: In diabetic UT knockout mice, expression of LC3-II is increased and p62 was reduced in comparison with that of the normal diabetic mice. Fibronectin and collagen IV were downregulated in diabetic UT knockout mice when compared with that of the normal diabetic mice. For the in vitro cell experiment, UII was shown to inhibit expression LC3-II and increase expression of p62 in comparison with that of the normal control. Treatment with SB-657510 can block UII-induced downregulation of LC3-II and upregulation of p62 while inhibiting UII-induced upregulation of fibronectin and collagen IV. Adding autophagy inducer, rapamycin, also inhibited UII-induced upregulation of fibronectin and collagen IV. CONCLUSIONS: The present study is the first to show that UII can downregulate autophagy in the kidney while accompanying the increased production of extracellular matrix in early diabetes. Our in vitro study also showed that upregulation of autophagy can decrease UII-induced production of extracellular matrix in HK-2 cells.