Effects of intravenous sodium thiosulfate on vascular calcification in dialysis patients with end-stage renal disease: a systematic review and meta-analysis.

BACKGROUND: In dialysis patients, vascular calcification is a common complication and is closely related to the morbidity and mortality of cardiovascular disease. We performed a systematic review to determine the efficacy and safety of sodium thiosulfate (STS) in the progression of vascular calcification in dialysis patients with end-stage renal disease. METHODS: The PubMed, Web of Science, Embase, Cochrane Library, Wanfang, CNKI, China Biology Medicine disc and Weipu databases were searched up to 9 March 2022 for clinical trials to synthesise findings on the efficacy and safety of STS in the progression of vascular calcification in dialysis patients. The primary outcome was coronary artery calcification scores (CACS) or abdominal aortic calcification scores (AACS) or Kauppila index. The secondary outcome was pulse-wave velocity (PWV). Laboratory data were shown in safety data. A random-effect model was used to provide the summary measures of effect [standardised mean difference (SMD) and 95% confidence interval (CI)]. RESULTS: Seven randomised, controlled trials and one nonrandomised, controlled trial involving 370 patients were included. Six studies reported that the progression of CACS or AACS was slower in the intravenous STS group compared with the control group (SMD -3.24, 95% CI: -5.29, -1.18, p = 0.002). Two studies showed the increase in PWV was less in the STS group compared with the control group (SMD -0.52, 95% CI: -0.92, -0.13, p = 0.009). During the trial period, a lower high-sensitivity C-reactive protein level (SMD 1.61, 95% CI: 0.19, 3.04, p = 0.03), a decrease in serum bicarbonate level (SMD 0.67, 95% CI: 0.22, 1.11, p = 0.003) and an increase in serum phosphate level (SMD -0.32, 95% CI: -0.62, -0.03, p = 0.03) were noted in the intravenous STS group compared with the control group. However, serum calcium and parathyroid hormone levels showed no difference between the two groups after the trials. The most common adverse events were temporary nausea and vomiting, which occurred in 12.5 to 75% of patients. CONCLUSIONS: Intravenous STS may slow down the progression of vascular calcification and ameliorate arterial stiffness in dialysis patients. Reliably defining the efficacy and safety of intravenous STS in attenuating the progression of vascular calcification requires a high-quality trial with a large sample size.

Minimal change disease associated with gastrointestinal stromal tumor accompanied by significantly elevated serum IgE level: a case report.

BACKGROUND: Minimal change disease (MCD) is a common cause of the nephrotic syndrome. Several studies have shown an increased incidence of cancer in patients with MCD. However, there are no reports on the association between MCD and gastrointestinal stromal tumor (GIST). CASE PRESENTATION: We report a case of a 66-year-old female with severe nephrotic syndrome and concomitant duodenal GIST. Immunoglobulin test showed a significant increase of IgE levels. The diagnosis of renal histopathology was MCD with subacute tubulointerstitial injury. The combination of preoperative Imatinib mesylate chemotherapy and tumor excision was accompanied by significant remission of proteinuria, and IgE level decreasing, without immunosuppressivetherapy. CONCLUSIONS: It is the first case report that MCD was associated with GIST and elevated IgE level. Clinically, in patients with elevated IgE level associated with nephrotic syndrome, the possibility of tumor must be taken into account when allergic factors are excluded.

The Clinical Characteristics and Antihypertensive Medications for Mortality of Elderly Hospitalized Hemodialysis patients: a Multicenter Retrospective Study in China.

This study aimed to evaluate the clinical characteristics and antihypertensive medications affecting elderly hemodialysis (HD) patient mortality. This retrospective cohort study enrolled patients (≥18 years old) discharged from 15 tertiary general hospitals in China between January 1, 2009, and December 31, 2011. The characteristics of elderly HD patients (≥60 years old) and antihypertensive medications for mortality were analyzed. A total of 7135 patients on maintenance HD, including 2738 elderly patients, were enrolled in this study. The mean levels of hemoglobin, albumin, serum calcium, phosphorus, and parathyroid hormone in elderly group were lower than the younger group (P <0.05). The top two reasons for the hospitalization of elderly patients were infection and cardiovascular disease (CVD). We compared the characteristics of 2492 survived elderly maintenance HD patients and 246 patients who died. Aging [odds ratio OR = 1.59, 95% confidence interval (CI): 1.13-2.24] and central venous catheter (CVC) (OR = 1.62, 95% CI: 1.53-1.72) were independently risk factors for mortality in elderly maintenance HD patients. Maintenance HD patients with high levels of hemoglobin (OR = 0.76, 95% CI: 0.73-0.79), albumin (OR = 0.87, 95% CI: 0.77-0.98), uric acid (OR = 0.90, 95% CI: 0.84-0.9) and those taking angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker (OR = 0.77, 95% CI: 0.58-0.90) had a lower risk of mortality. Other antihypertensive drugs including: ß-blockers, calcium channel blockers, and α-blockers were not significantly associated with mortality (P >0.05). CVD and infection were the most common causes of hospitalization and/or mortality in elderly HD patients. Age, anemia and malnutrition, use of CVCs, and low level of serum uric acid are the risk factors for mortality in elderly maintenance HD patients. Renin-angiotensin system blockade might provide a benefit in protecting elderly maintenance HD patients from mortality.

Risk factors for mortality in elderly haemodialysis patients: a systematic review and meta-analysis.

BACKGROUND: Older haemodialysis patients accompany a high burden of functional impairment, limited life expectancy, and healthcare utilization. This meta-analysis aimed to evaluate how various risk factors influenced the prognosis of haemodialysis patients in late life, which might contribute to decision making by patients and care providers. METHODS: PubMed, Embase, and Cochrane Central were searched systematically for studies evaluating the risk factors for mortality in elderly haemodialysis patients. Twenty-eight studies were included in the present systematic review. The factors included age, cardiovascular disease, diabetes mellitus, type of vascular access, dialysis initiation time, nutritional status and geriatric impairments. Geriatric impairments included frailty, cognitive or functional impairment and falls. Relative risks with 95% confidence intervals were derived. RESULTS: Functional impairment (OR = 1.45, 95% CI: 1.20-1.75), cognitive impairment (OR = 1.46, 95% CI: 1.32-1.62) and falls (OR = 1.14, 95% CI: 1.06-1.23) were significantly and independently associated with increased mortality in elderly haemodialysis patients. Low body mass index conferred a mortality risk (OR = 1.43, 95% CI: 1.31-1.56) paralleling that of frailty as a marker of early death. The results also confirmed that the older (OR = 1.43, 95% CI: 1.22-1.68) and sicker (in terms of Charlson comorbidity index) (OR = 1.41, 95% CI: 1.35-1.50) elderly haemodialysis patients were, the more likely they were to die. In addition, increased mortality was associated with early-start dialysis (OR = 1.18, 95% CI: 1.01-1.37) and with the use of a central venous catheter (OR = 1.53, 95% CI: 1.44-1.62). CONCLUSIONS: Multiple factors influence the risk of mortality in elderly patients undergoing haemodialysis. Geriatric impairment is related to poor outcome. Functional/cognitive impairment and falls in elderly dialysis patients are strongly and independently associated with mortality.

Therapeutic effect of intravenous sodium thiosulfate for uremic pruritus in hemodialysis patients.

OBJECTIVES: This study aimed to compare the efficacy of intravenous sodium thiosulfate (IV STS) with that of loratadine in the treatment of uremic pruritus in hemodialysis (HD) patients. METHODS: This retrospective study included 44 HD patients with pruritus aged over 18 years between June 2018 and January 2020 at the Aerospace Center Hospital of China. Twenty-four HD patients received 3.2 g IV STS treatment three times per week at the end of each HD session for 8 weeks. Twenty HD patients received loratadine (10 mg/day) for 8 weeks. Pruritus intensity was measured using a visual analog scale (VAS) and the detailed pruritus score (DPS) at three time points. The safety of STS was evaluated according to adverse event symptoms and biological variable changes. RESULTS: There was no significant difference between the STS and loratadine groups in age, sex, characteristics of pruritus, or other clinical variables before treatment. After 8 weeks of treatment, the VAS score (7.07 ± 2.56 and 2.67 ± 2.01) and DPS (30.72 ± 4.81 and 8.04 ± 2.86) decreased significantly in the STS group (p < 0.05). The mean decrease in VAS score (6.89 ± 1.98 and 6.34 ± 2.35) and DPS (28.90 ± 3.24 and 26.92 ± 2.41) in the loratadine group was not statistically significant (p > 0.05). There were no morbidities or mortalities associated with the use of either drug. All biological variables remained stable after therapy. CONCLUSIONS: STS can improve uremic pruritus in HD patients. However, literature on the subject remains lacking. Close monitoring for adverse effects is advised.

Cognitive impairment and associated risk factors in older adult hemodialysis patients: a cross-sectional survey.

The clinical epidemiological features of cognitive impairment in Chinese older adult patients undergoing hemodialysis are not clear, we aimed to identify the extent and patterns of cognitive impairment among those patients. We conducted a cross-sectional study of 613 hemodialysis patients aged 50 to 80 from 11 centers in Beijing. A neuropsychological battery of 11 tests covering domains of attention/processing speed, executive function, memory, language, and visuospatial function was applied, patients were classified as none, mild, or major cognitive impairment according to the fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria for cognitive impairment. Compared with Chinese population norms, 37.2% of the participants had mild cognitive impairment, 43.7% had major cognitive impairment. Memory and language were the most severe impaired domains in the mild cognitive impairment group, attention and visuospatial function domains were the most serious impaired domains in the major cognitive impairment group. Concomitant impairment across multiple cognitive domains was common. Factors associated with major cognitive impairment included age, education level, history of stroke and hypertension, dialysis vintage, and single-pool Kt/V. There is a high frequency of cognitive impairment in Chinese older adult hemodialysis patients, with varying severity and concomitant impairment across multiple domains.

Can we predict who will develop postoperative hyperkalaemia after parathyroidectomy in dialysis patients with secondary hyperparathyroidism?

BACKGROUND: Hyperkalaemia occurs frequently in many maintenance haemodialysis (MHD) patients after parathyroidectomy (PTX) with secondary hyperparathyroidism (SHPT). However, the clinical risk factors that predict postoperative hyperkalaemia are uncertain. METHODS: This retrospective cohort study included 90 maintenance haemodialysis patients aged ≥18 years who underwent PTX between April 2011 and April 2016 at Aerospace Center Hospital (Peking University Aerospace School of Clinical Medicine). Pre- and post-PTX surgery venous samples were measured in quadruplicate. We examined univariate associations with demographics, dialysis characteristics, laboratory values and medications. Hyperkalaemia was defined as serum potassium >5.3 mmol/L. RESULTS: Out of nighty patients, twenty-two (24.4%) developed postoperative hyperkalaemia, of whom sixteen (18.1%) developed hyperkalaemia on postoperative day 3. The univariate analysis showed that weight, dialysis duration, preoperative serum potassium, alkaline phosphate, triglyceride, and postoperative alkaline phosphate were independently associated with hyperkalaemia after parathyroidectomy. The univariate logistic regression model showed that preoperative serum potassium was the only independent factor that could predict hyperkalaemia after parathyroidectomy (odds ratio, 1.59; 95% confidence interval, 1.24-2.05). The optimal cut-off for pre-operative K was 3.9 mmol/L according to the receiver operating characteristic (ROC) curve. A higher incidence of postoperative hyperkalaemia was found in male and younger patients, but the difference was not statistically significant (p>0.05). CONCLUSIONS: Pre-operative serum potassium less than 3.9 mmol/L was associated with less hyperkalaemia post-operatively in end-stage renal disease (ESRD) patients undergoing PTX.

Impact of Different Levels of iPTH on All-Cause Mortality in Dialysis Patients with Secondary Hyperparathyroidism after Parathyroidectomy.

BACKGROUND: Secondary hyperparathyroidism (SHPT) usually required parathyroidectomy (PTX) when drugs treatment is invalid. Analysis was done on the impact of different intact parathyroid hormone (iPTH) after the PTX on all-cause mortality. METHODS: An open, retrospective, multicenter cohort design was conducted. The sample included 525 dialysis patients with SHPT who had undergone PTX. RESULTS: 404 patients conformed to the standard, with 36 (8.91%) deaths during the 11 years of follow-up. One week postoperatively, different levels of serum iPTH were divided into four groups: A: ≤20 pg/mL; B: 21-150 pg/mL; C: 151-600 pg/mL; and D: >600 pg/mL. All-cause mortality in groups with different iPTH levels appeared as follows: A (8.29%), B (3.54%), C (10.91%), and D (29.03%). The all-cause mortality of B was the lowest, with D the highest. We used group A as reference (hazard ratio (HR) = 1) compared with the other groups, and HRs on groups B, C, and D appeared as 0.57, 1.43, and 3.45, respectively. CONCLUSION: The all-cause mortality was associated with different levels of iPTH after the PTX. We found that iPTH > 600 pg/mL appeared as a factor which increased the risk of all-cause mortality. When iPTH levels were positively and effectively reducing, the risk of all-cause mortality also decreased. The most appropriate level of postoperative iPTH seemed to be 21-150 pg/mL.

Efficacy and safety of calcineurin inhibitor treatment for IgA nephropathy: a meta-analysis.

BACKGROUND: IgA nephropathy is the most common progressive glomerular disease to end stage renal failure worldwide. Calcineurin inhibitors (CNIs) is a selective immunosuppressant widely used in organ transplantation. The efficacy and safety of calcineurin inhibitors for the treatment of IgA nephropathy remain uncertain. METHODS: We performed a systematic literature search using the PubMed, Embase, Science Citation Index, Ovid evidence-based medicine, Chinese Biomedical Literature (CBM) and Chinese science and technology periodicals (CNKI, VIP, and Wan Fang) for randomized, controlled trials of CNIs therapy of IgA nephropathy. Complete remission rate (CR) was defined as proteinuria less than 0.5 or 0.3 g/d. Partial remission rate (PR) was defined as proteinuria reduced to at least half of the baseline measurement and an absolute value of >0.5 or 0.3 g/d. RESULTS: Seven relevant trials were conducted with 374 patients enrolled. CNIs plus medium/low-dose steroid had a higher CR (RR = 2.51 [95% CI,1.25 to 5.04], P = 0.02) compared to therapy with steroid alone or placebo, but were not significant on PR (RR = 0.87 [95% CI,0.32 to 2.38]; P = 0.78). Also, significant alterations were observed in proteinuria (weighted mean difference, -0.46 g/d,[95% CI:-0.55 to -0.24], P < 0.01) with no differences were found in serum creatinine (SCr) (weighted mean difference, 0.57,95% CI:-4.05 to 5.19; P = 0.78) and estimated glomerular filtration rate (eGFR) (weighted mean difference, 1.13,95% CI:-4.05 to 6.32; P = 0.34) level between the two groups. CNI therapy was associated with an increased risk for adverse events (RR = 2.21,95% CI:1.52 to 3.21, P < 0.01), such as gastrointestinal and neurological symptoms or hirsutism. CONCLUSIONS: CNIs might provide renal protection in patients with IgAN, but at an increased risk of adverse events. Reliably defining the efficacy and safety of CNIs in IgAN requires a high-quality trial with a large sample size.

[Evaluation of optimal dosage of heparin in hemodialysis patients by thromboelastograph].

OBJECTIVE: To assess the blood coagulation function and investigate the appropriate dose of unfractionated heparin by thromboelastograph in maintenance hemodialysis (MHD) patients. METHODS: Thirty MHD patients were enrolled in this study and divided into two groups. The total dose of unfractionated heparin was below 80 u/kg in the low-dose group (LH, n=16), while it exceeded 80 u/kg in the high-dose group (HH, n=14). Blood routine tests and conventional coagulation examinations were measured before hemodialysis. TEG and activated partial thromboplastin time (APTT) were examined at the beginning and the end of hemodialysis at the arterial circuit, and the second hour (h 2) at the venous circuit. RESULTS: The initial bolus dose of unfractionated heparin for LH and HH groups were (26.6±6.2) u/kg vs. (42.3±8.2) u/kg and the repeated maintenance dose for both the groups were (13.7±5.1) u/kg/h vs. (18.2±4.3) u/kg/h. No significant difference was noticed in results from blood routine tests and conventional coagulation parameters between the two groups. In LH group, the increase of APTT at h 2 of hemodialysis was significant compared with the baseline, while it recovered partly at the end of hemodialysis. R value prolonged at h 2 and the end of hemodialysis. CI value was more negative at the end of hemodialysis. In HH group, APTT obviously prolonged at h 2 and the end of hemodialysis. R value also obviously prolonged at h 2 of hemodialysis. At the end of hemodialysis, R and K values prolonged, MA value reduced, and CI value was more negative. APTT was significantly different between the two groups at h 2 of hemodialysis. At the end of hemodialysis, APTT was still extended in HH group, but there was no significant difference. R value at h 2, and R, K, MA, CI values at the end of hemodialysis were significantly different between the two groups. R values at the end of hemodialysis had a direct correlation with the dose of unfractionated heparin (r=0.403, P=0.041), but APTT had not. There was no significant difference in transmembrane pressure, venous pressure and filter clotting between the two groups. CONCLUSION: Low-dose heparin is effective and safe as anticoagulant in hemodialysis. TEG shows that the blood coagulation function is more sensitive than conventional coagulation parameters and is useful to anticoagulant therapy in MHD patients.

[High glucose downregulates the expression of podocalyxin protein in glomerular podocytes of mice].

OBJECTIVE: To examine the expression of podocalyxin protein in glomerular podocytes by long-term high glucose exposure in vitro and in vivo. METHODS: Immunohistochemical staining and computer image analysis were applied to detect the expression of podocalyxin protein in glomeruli from db/db mice and Wt mice. The effects of high glucose on the expression of podocalyxin protein were analyzed by Western blotting. The activation of MAPKS signaling pathway (ERK, p38 and JNK) by high glucose was also examined. RESULTS: The expressions of podocalyxin protein in db/db mice were obviously less than that in Wt mice [(0.18+/-0.07) vs (0.25+/-0.05),P<0.05] assessed by immunostaining and semiquantitative analysis. Basal levels of podocalyxin protein were observed in cultured mouse podocytes. The level of podocalyxin protein declined at each time point by high glucose incubation, reached the lowest level on the 6th day (5.5% of control group, P<0.01), but no significant changes were observed in normal glucose and mannitol glucose incubation groups. High glucose medium induced phosphorylation of ERK1/2 as early as 30 minutes, reached the peak at hour 6; maintained the activation from hour 12 to 24, and declined to the basal level at hour 48. However, activation of ERK1/2 was not detected in normal glucose and mannitol glucose groups. Blockade of activation of ERK1/2 with PD98059, a specific ERK1/2 activation inhibitor, attenuated the high glucose-induced expression of podocalyxin protein on the 6th day. CONCLUSION: High ambient glucose decreases the protein level of podocalyxin by podocyte in vitro and in vivo, and the decrease in podocalyxin protein is ERK1/2jdependent in cultured podocytes.

[High glucose regulates the expression of connective tissue growth factor and its receptor (low density lipoprotein receptor-related protein) in cultured podocytes].

OBJECTIVE: To observe the expression of connective tissue growth factor (CTGF) and its receptor-low density lipoprotein receptor-related protein (LRP), and the relevant signaling pathway for the regulation by long-term high glucose exposure in cultured podocytes. METHODS: The effects of high glucose on the expression of CTGF and its receptor LRP were analyzed by western blotting. The activation of mitogen activated protein kinase (MAPKS) signaling pathway by high glucose was also examined. RESULTS: Basal levels of CTGF were observed in cultured mouse podocytes, the levels of CTGF protein were increased by high glucose medium groups on the 2nd day, reached the peak on the 4th day (P< 0.05), began to decline on the 6th day, returned to the basal level on the 8th day (P>0.05). The levels of CTGF expression in normal glucose and mannitol glucose groups did not change markly. High glucose medium induced phosphorylation of ERK1/2 at as early as minute 30, reached the peak at hour 6; maintained the activity at hours 12 and 24, and declined to the basal level at hour 48. However, phosphorylation of ERK1/2 was not detected in normal glucose and mannitol glucose groups. Blockade of phosphorylation of ERK1/2 with PD98059, a specific ERK1/2 activation inhibitor, did decrease the high glucose-triggered expression of CTGF protein in 4 days. High glucose had no effect on the expression of LRP protein at each time point. CONCLUSION: Acute high glucose (2-4 days) stimulated the expression of CTGF protein via ERK1/2-dependent signaling pathway in cultured podocytes, while cultured in high glucose for 6-8 days, the podocytes did not increase its CTGF level. Long-term high glucose had no effect on the expression of LRP in podocytes.