Exogenous biological renal support ameliorates renal pathology after ischemia reperfusion injury in elderly mice.

We established an exogenous biological renal support model through the generation of parabiotic mice. At 72 hours after ischemia reperfusion injury (IRI), the aged mice that received exogenous biological renal support showed significantly higher levels of renal cell proliferation and dedifferentiation, lower levels of renal tubular injury, improved renal function, and a lower mortality than those that did not receive exogenous biological renal support. Using the Quantibody Mouse Cytokine Antibody Array, we found that aged IRI mice that received exogenous biological renal support had an up-regulation of multiple inflammatory related cytokines compared to the group that did not receive exogenous biological renal support. We suggest that the exogenous biological renal support might promote renal tubular epithelial cell proliferation and dedifferentiation and improve the prognosis of aged IRI mice. Exogenous biological renal support may play an important role in the amelioration of renal IRI by regulating the expression of multiple cytokines.

Impacts of parathyroidectomy on calcium and phosphorus metabolism disorder, arterial calcification and arterial stiffness in haemodialysis patients.

BACKGROUND: Secondary hyperparathyroidism (SHPT) and calcium and phosphorus metabolism disorder are important complications in haemodialysis patients. Parathyroidectomy (PTX) may prevent or delay the progress of vascular calcification in haemodialysis patients. OBJECTIVE: To investigate the impacts of PTX on calcium and phosphorus metabolism, arterial calcification and arterial stiffness in haemodialysis patients with SHPT. METHODS: Twenty-one SHPT-haemodialysis patients were selected for PTX. The preoperative and postoperative 1-year scores of coronary artery calcification were measured via multislice spiral CT, along with the brachial-ankle pulse wave velocity (baPWV), and preoperative and postoperative 1-year indexes such as calcium, phosphorus, calcium-phosphorus product concentration and parathyroid hormone (PTH) level were compared. RESULTS: Compared with the preoperative score, the postoperative 1-year coronary artery calcification score was significantly reduced; the mean baPWVs of the bilateral limbs were reduced; and the levels of serum calcium, phosphorus, calcium-phosphorus product concentration and PTH were all reduced; all differences were statistically significant (P < 0.05). CONCLUSIONS: PTX can be used to correct calcium and phosphorus metabolism disorder, reduce arterial calcification, and improve arterial stiffness.

Youthful systemic milieu alleviates renal ischemia-reperfusion injury in elderly mice.

The incidence of acute kidney injury (AKI) is high in elderly people, and is difficult to prevent and treat. One of its major causes is renal ischemia-reperfusion injury (IRI). A young systemic environment may prevent the senescence of old organs. However, it is unknown whether a young milieu may reduce renal IRI in the elderly. To examine this question, bilateral renal IRI was induced in old (24 months) mice three weeks after parabiosis model establishment. At 24 hours after IRI, compared to old wild-type mice, the old mice with IRI had significantly damaged renal histology, decreased renal function, increased oxidative stress, inflammation, and apoptosis. However, there was no increase in autophagy. Compared to old mice with IRI, old-old parabiosis mice with IRI did not show differences in renal histological damage, oxidative stress, inflammation, apoptosis, or autophagy, but did exhibit improved renal function. Compared to the old-old parabiosis mice with IRI, the old mice with IRI in the young (12 week)-old parabiosis showed less renal histological injury and better renal function. Renal oxidative stress, inflammation, and apoptosis were significantly decreased, and autophagy was significantly increased. Thus, a youthful systemic milieu may decrease oxidative stress, inflammation, and apoptosis, and increase autophagy in old mice with IRI. These effects ameliorated IRI injuries in old mice. Our study provides new ideas for effectively preventing and treating AKI in the elderly.

Efficacy of Leflunomide, Telmisartan, and Clopidogrel for Immunoglobulin A Nephropathy: A Randomized Controlled Trial.

BACKGROUND: The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN. METHODS: It is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan (80 mg/d) wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo (Group A), 50 mg/d clopidogrel (Group B), 20 mg/d leflunomide (Group C), or 50 mg/d clopidogrel and 20 mg/d leflunomide (Group D). The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry. RESULTS: The effects of telmisartan combined with leflunomide on changes in proteinuria (0.36 [95% confidence interval (CI) 0.18-0.55] g/d, P < 0.001), in serum uric acid (76.96 [95% CI 57.44-96.49] µmol/L, P < 0.001), in serum creatinine (9.49 [95% CI 6.54-12.44] µmol/L, P < 0.001), and in estimated glomerular filtration rate (-6.72 [95% CI-9.46 to -3.98] ml·min-1·1.73 m-2, P < 0.001) were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight (P > 0.05). Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed. CONCLUSIONS: Telmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients. TRIAL REGISTRATION: chictr.org.cn, ChiCTR-TRC-10000776; http://www.chictr.org.cn/showproj.aspx?proj=8760.

Telmisartan combined with probucol effectively reduces urinary protein in patients with type 2 diabetes: A randomized double-blind placebo-controlled multicenter clinical study.

BACKGROUND: Persistent proteinuria is an important factor contributing to the progression of diabetic nephropathy. The present randomized double-blind placebo-controlled multicenter clinical study evaluated the efficacy and safety of telmisartan combined with the antioxidant probucol in reducing urinary protein levels in patients with type 2 diabetes (T2D). METHODS: Patients with T2D and 24-h proteinuria 0.5-3 g were enrolled in the study and randomly assigned to one of two groups: a telmisartan or a probucol + telmisartan group. Both groups were given telmisartan 80 mg q.d. for 48 weeks. The probucol + telmisartan group was given probucol 500 mg b.i.d. for the first 24 weeks, with the dosage then reduced to 250 mg b.i.d. for the remaining 24 weeks. The telmisartan group was given probucol placebo. RESULTS: In all, 160 patients were enrolled in the present study. The 24-h proteinuria levels were significantly reduced in the probucol + telmisartan compared with telmisartan group. For patients with baseline 24-h proteinuria levels <1.0 g, both treatments resulted in significant reductions in 24-h proteinuria levels after 48 weeks treatment. However, in patients with baseline 24-h proteinuria levels ≥1.0 g, 24-h proteinuria levels after 48 weeks treatment were only reduced in the probucol + telmisartan group. There was no significant difference between the two groups for either adverse cardiovascular or other events. CONCLUSIONS: In patients with diabetic nephropathy, probucol combined with telmisartan more effectively reduces urinary protein levels than telmisartan alone.

Low calcium dialysate combined with CaCO3 in hyperphosphatemia in hemodialysis patients.

This aim of this study was to observe the effects of the application of low calcium dialysate (LCD) combined with oral administration of CaCO3 in the treatment of hyperphosphatemia, as well as blood Ca2+, calcium-phosphate product (CPP), parathyroid hormone (PTH) and blood pressure in patients undergoing hemodialysis. Thirty-one maintenance hemodialysis (MHD) patients with hyperphosphatemia, but normal blood Ca2+, underwent dialysis with an initial dialy-sate Ca2+ concentration (DCa) of 1.50 mmol/l for six months and then with 1.25 mmol/l for six months. The patients who underwent dialysis with a DCa of 1.25 mmol/l were treated orally with 0.3 g CaCO3 tablets three times a day. In the third and sixth months [observation end point (OEP)] of the dialysis, the concentrations of Ca2+, phosphorus and intact PTH (iPTH) were measured; blood pressure and side-effects prior to and following dialysis were also observed. The Ca2+, CPP and iPTH levels increased (P<0.05) in the sixth month of treatment with a DCa of 1.50 mmol/l. However, the Ca2+ concentration declined to a certain degree, CPPs decreased significantly (P<0.05) and the iPTH concentration increased following treatment with a DCa of 1.25 mmol/l for six months. The incidence rate of adverse effects of LCD was 12.9% (4/31); the effects were mainly muscle spasms, hypotension and elevated PTH. The periodic application of LCD combined with the oral administration of CaCO3 effectively reduced serum phosphorus and CPPs among MHD patients with hyperphosphatemia, indicating that the treatment may be used clinically.

The clinical significance and risk factors of anti-platelet factor 4/heparin antibody on maintenance hemodialysis patients: a two-year prospective follow-up.

BACKGROUND: Heparin-induced thrombocytopenia is an immune response mediated by anti-PF4/heparin antibody, which is clinically characterized by thrombocytopenia and thromboembolic events. In this study, a prospective and multi-center clinical investigation 1) determined the positive rate of anti-PF4/heparin antibody in maintenance hemodialysis patients in China, 2) identified the related risk factors, and 3) further explored the effect of the anti-PF4/heparin antibody on bleeding, thromboembolic events, and risk of death in the patients. METHODS: The serum anti-PF4/heparin antibody was measured in 661 patients from nine hemodialysis centers, detected by IgG-specific ELISA and followed by confirmation with excess heparin. Risk factors of these patients were analyzed. Based on a two-year follow-up, the association between the anti-PF4/heparin antibody and bleeding, thromboembolic events, and risk of death in the patients was investigated. RESULTS: 1) The positivity rate of the anti-PF4/heparin antibody in maintenance hemodialysis patients was 5.6%. With diabetes as an independent risk factor, the positivity rate of the anti-PF4/heparin antibody decreased in the patients undergoing weekly dialyses ≥3 times. 2) The positivity rate of the anti-PF4/heparin antibody was not related to the occurrence of clinical thromboembolic events and was not a risk factor for death within two years in maintenance hemodialysis patients. 3) Negativity for the anti-PF4/heparin antibody combined with a reduction of the platelet count or combined with the administration of antiplatelet drugs yielded a significant increase in bleeding events. However, the composite determination of the anti-PF4/heparin antibody and thrombocytopenia, as well as the administration of antiplatelet drugs, was not predictive for the risk of thromboembolic events in the maintenance hemodialysis patients. CONCLUSIONS: A single detection of the anti-PF4/heparin antibody did not predict the occurrence of clinical bleeding, thromboembolic events, or risk of death in the maintenance hemodialysis patients.

Mortality rates among prevalent hemodialysis patients in Beijing: a comparison with USRDS data.

BACKGROUND: The raw annual mortality rate reported in Chinese patients on maintenance hemodialysis (MHD) was around 10% between 2005 to 2010, and it was around 20% in the US as reported by the United States Renal Data System (USRDS). Our hypothesis was that the large survival difference was caused by differences in race and practice pattern between nations in addition to differences in patient characteristics. METHODS: Annual mortality in Beijing prevalent MHD patients per year in 2007, 2008, 2009 and 2010 was reported and relative risks of death were compared with the corresponding mortality of USRDS prevalent MHD patients (in whites, African-Americans and Asian-Americans) after age, gender and primary cause of end-stage renal disease (ESRD) were adjusted. A total of 11 675 MHD patients from 104 dialysis facilities under control of Beijing Blood Purification Quality Control and Improvement Center (BJBPQCIC) from 31 December 2006 to 31 December 2010 were included. A total of 1 937 819 MHD patients (only white, African-American and Asian-American were eligible for inclusion) were subtracted from the USRDS No-60-Day prevalent dataset from the year 2004 to 2009, using the RenDER system. Raw annual mortality for each race was reported as a number per 1000 MHD patients at risk for each year. Age, gender and primary cause of ESRD, adjusted annual mortality and relative risk race of death were reported comparing the Beijing patients and each race of the USRDS. RESULTS: The raw annual mortality for the Beijing cohort increased gradually from 47.8 per 1000 patient-years in 2007 to 76.8 in 2010. The raw annual mortality for the white cohort in 2007 was 250.7 per 1000 patient-years, and gradually decreased to 236.3 in 2009. The raw annual mortality for African-Americans (167.8 and 156.7 per 1000 patient-years in 2007 and 2009, respectively) was much lower than that for whites. The annual mortality for Asian-Americans was slightly lower than that for African-Americans. After adjustment, Beijing MHD still had a survival benefit compared with each of the examined USRDS race. The annual mortality rates were 99.4, 80.6 and 94.3 per 1000 patient-years when adjusted to whites, African-Americans and Asian-Americans, respectively, in cohort 2009. CONCLUSIONS: The annual mortality for the Beijing MHD patients was lower than that for their USRDS counterparts, and this difference existed after baseline demographics were adjusted. This survival difference between the Beijing and the USRDS MHD cohorts could be attributed to differences in race or practice pattern. More studies are needed to validate our hypothesis.

International study on Sagliker syndrome and uglifying human face appearance in severe and late secondary hyperparathyroidism in chronic kidney disease patients.

OBJECTIVE: It is known that skeletal changes due to secondary hyperparathyroidism (SH) can be severe in chronic kidney disease (CKD). Recently described Sagliker syndrome (SS) is a very striking and prominent feature of SH in CKD, including an uglifying appearance to the face, short stature, extremely severe maxillary and mandibulary changes, soft tissue in the mouth, teeth/dental abnormalities, fingertip changes, knee and scapula deformities, hearing abnormalities, and neurological and, more important, severe psychological problems. DESIGN, SETTING, PATIENTS: In the past 8 years, we have encountered 40 cases of SS in SH and CKD by performing an international study in Turkey, India, Romania, Egypt, Maleysia, Tunis, and China. RESULTS: The medical history of these patients showed that they did not receive proper therapy. Changes, particularly in children and teenagers, become irreversible, which was disastrous for the patients both aesthetically and psychologically. CONCLUSION: Treatment must begin early and be the appropriate treatment given in centers with sophisticated skills. Otherwise, the inability to correct all the changes in the skull and face, to remodel a new face, to extending the height, and, most important, to convince the patients to face the dramatic psychological problems can be catastrophic for those patients.