Association of Serum Sclerostin Level, Coronary Artery Calcification, and Patient Outcomes in Maintenance Dialysis Patients.

OBJECTIVE: The objective of this study is to investigate the association between the serum sclerostin, the coronary artery calcification (CAC), and patient outcomes in maintenance dialysis patients. METHODS: We performed a prospective cohort study of 65 maintenance dialysis patients in 2014, including 39 patients on peritoneal dialysis and 26 on hemodialysis, and followed up for 5 years. Parameters of mineral metabolism including bone-specific alkaline phosphatase, fibroblast growth factor 23, sclerostin, and other biochemical factors were determined at the baseline. Meanwhile, the CAC score was analyzed by cardiac computed tomography. RESULTS: Serum sclerostin in hemodialysis patients was significantly higher than that in peritoneal dialysis patients (632.35 ± 369.18 vs. 228.85 ± 188.92, p < 0.001). The patients with CAC were older, receiving hemodialysis, lower Kt/V, and had longer dialysis vintage, as well as higher levels of serum 25-(OH)-vit D and sclerostin. In multivariate logistic regression analysis, older age and lower Kt/V were risk factors for CAC. The area under the receiver operating characteristic curves for prediction of CAC by sclerostin was 0.74 (95% confidence interval 0.605-0.878, p = 0.03), and the cutoff value of sclerostin is 217.55 pg/mL with the sensitivity 0.829 and specificity 0.619. After 5 years of follow-up, 51 patients survived. The patients in the survival group had significantly lower age, sclerostin levels, and low CAC scores than the nonsurvival group. Old age (≥60 years, p < 0.001) and high CAC score (≥50 Agatston unit, p = 0.031) were significant risk factors for the patient survival. CONCLUSIONS: Sclerostin is significantly elevated in dialysis patients with CAC. But sclerostin is not a risk factor for CAC. After 5 years of follow-up, patients in the survival group are younger and have lower sclerostin levels and CAC scores. But sclerostin levels are not independent risk factors for high mortality in dialysis patients.

Ratio of Overhydration and Extracellular Water Versus Ratio of Extracellular Water and Body Cell Mass in the Assessment of Fluid Status in Patients With Acute Kidney Injury Requiring Kidney Replacement Therapy: A Cohort Study.

OBJECTIVES: The aim of this study is to analyze the association between the ratio of overhydration and extracellular water (OH/ECW) and the ratio of extracellular water and body cell mass (ECW/BCM) measured by bioelectrical impedance and outcomes of patients with acute kidney injury (AKI) requiring kidney replacement therapy (KRT). METHODS: Patients with severe AKI treated with KRT in our hospital between September 2016 and August 2018 were enrolled. These patients were assessed using a body composition monitor before KRT, and on the 3rd day and the 7th day after initiation of KRT. The predictors mainly included OH/ECW and ECW/BCM. The association between all-cause mortality and predictors were analyzed using Cox regression. RESULTS: A total of 152 patients were included in this study with a median follow-up of 39 (interquartile range 8-742) days. The 28-day mortality, 90-day mortality, and 1-year mortality were 46.7%, 54.6%, and 60.5%, respectively. A high ratio of OH/ECW (adjusted hazard ratio per standard deviation, 1.45; 95% confidence interval = 1.15-1.82, P = .002) and a high ratio of ECW/BCM (adjusted hazard ratio per standard deviation, 1.33, 95% confidence interval = 1.07-1.64, P = .009) before KRT were associated with all-cause mortality during follow-up. Higher ECW/BCM rather than OH/ECW at 7th day was associated with poorer outcomes. Furthermore, a reduction of OH/ECW with an increase of ECW/BCM had higher 1-year mortality as compared to others (85.7% vs. 51.2%, P = .004) in patients who survived 7 days after KRT initiation. CONCLUSIONS: ECW/BCM performed better than OH/ECW in assessment of fluid status in AKI patients requiring KRT. This study suggested that a simple reduction of OH/ECW without decreasing ECW/BCM may not improve outcomes.

Clinicopathological characteristics and outcome predictors of anti-glomerular basement membrane glomerulonephritis.

OBJECTIVE: To explore the clinicopathological features of anti-glomerular basement membrane (anti-GBM) glomerulonephritis (anti-GBM-GN) and the prognostic values of clinical and laboratory indicators at diagnosis on renal and patient survival. METHODS: A total of 76 patients (34 males and 42 females) with anti-GBM-GN who were hospitalized in the First Affiliated Hospital of Nanjing Medical University between January 2010 and June 2021 were included in this study. The baseline clinical features, histopathological data from renal biopsies, and predictors of renal and patient survival were retrospectively analyzed. RESULTS: Among the 76 patients, the median serum creatinine at diagnosis was 618.0 (350.98, 888.25) µmol/L and the median estimated glomerular filtration rate (eGFR) was 6.62 (4.39, 14.41) mL/min. Of these 76 patients, 55 (72.4%) received initial kidney replacement therapy (KRT) and 39 (51.3%) received plasma exchange or double-filtered plasmapheresis (DFPP). During a median follow-up duration of 28.5 (6.0, 71.8) months, 53 (69.7%) patients progressed to kidney failure with replacement therapy (KFRT) and received maintenance dialysis. Initial KRT (HR = 3.48, 95% CI = 1.22-9.97, p = 0.020) was a significant risk factor for renal survival. During the follow-up, 49 (64.5%) of 76 patients survived. Age (≥60 years, HR = 4.13, 95% CI = 1.65-10.38, p = 0.003) and initial KRT (HR = 2.87, 95% CI = 1.01-8.14, p = 0.047) were predictive of patient survival. CONCLUSIONS: Among patients with anti-GBM-GN, initial KRT at presentation was predictive of KFRT while older age and initial KRT were associated with higher all-cause mortality.

Body Composition Analysis as a Predictor of Prognosis for Patients With Acute Kidney Injury Requiring Kidney Replacement Therapy.

OBJECTIVES: The aim of this study is to investigate the association between body composition, measured by bioelectrical impedance analysis, and outcomes in patients with acute kidney injury (AKI) receiving kidney replacement therapy (KRT). METHODS: Patients with severe AKI treated with KRT in our hospital between September 2016 and August 2018 were enrolled. These patients were assessed by body composition analysis before KRT, and on the 3rd day and the 7th day after initiation of KRT. The predictors included lean tissue index (LTI), fat tissue index, and body cell mass index (BCMI). The association between all-cause mortality and predictors was analyzed using Cox regression. RESULTS: A total of 152 patients were included in this study, with a 28-day mortality of 46.7% and 1-year mortality of 60.5%. LTI (adjusted hazard ratio per standard deviation: 0.37; 95% confidence interval = 0.21-0.66, P < .001) and BCMI (adjusted hazard ratio per standard deviation: 0.37; 95% confidence interval = 0.21-0.67, P < .001) on day 7 after initiation of KRT, rather than before KRT, were associated with mortality during follow-up. LTI and BCMI before KRT were associated with 28-day mortality rather than 1-year mortality. CONCLUSIONS: LTI and BCMI before KRT were associated with short-term prognosis, and those on day 7 after KRT initiation were associated with intermediate mortality in patients with AKI requiring KRT.

Risk factors affecting renal function and survival of patients with myeloperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis
.

OBJECTIVE: To determine the prognostic values of clinical and laboratory features at the time of presentation on renal function and survival of patients with myeloperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis. (MPO-ANCA GN). MATERIALS AND METHODS: A total of 119 patients (52 males and 67 females) with MPO-ANCA GN and hospitalized at the First Affiliated Hospital of Nanjing Medical University from January 2010 to April 2018 were enrolled. The baseline clinical characteristics, renal biopsy pathological data, and risk factors predictive of renal and patient survival were retrospectively analyzed. RESULTS: Among these 119 patients, the median serum creatinine at diagnosis was 354.30 (range, 216.10 - 637.30) mmol/L and the median estimated glomerular filtration rate (eGFR) was 14.78 (range, 7.23 - 29.21) mL/min. In total, 58 (48.7%) patients received initial renal replacement therapy (RRT). During a median follow-up duration of 32 (range, 3 - 113) months, 57 (47.9%) patients progressed to end-stage renal disease (ESRD). Initial renal function status (i.e., initial RRT, serum creatinine, and eGFR) (p < 0.001) and hemoglobin level (p = 0.027) were significant risk factors for renal survival. During the follow-up, 69 (57.6%) of 119 patients survived. Age (p = 0.009) and urine red blood cell count (p = 0.012) were predictive of patient survival. CONCLUSION: Among patients with MPO-ANCA GN, poor renal function and lower hemoglobin level were predictive of ESRD, while older age and higher urinary red blood cell count were associated with a higher risk for all-cause mortality.

Comparison of microwave ablation treatments in patients with renal secondary and primary hyperparathyroidism.

Purpose: Microwave ablation (MWA) is feasible for severe renal secondary hyperparathyroidism (SHPT) and primary hyperparathyroidism (PHPT) patients ineligible for parathyroidectomy (PTX). Here we compared the clinical manifestations and characteristics of parathyroid glands in these two groups, and summarized the techniques, safety and efficacy of MWA.Methods: Baseline clinical characteristics, ablation-related techniques, adverse events/complications, and efficacy were recorded.Results: In SHPT group, malnutrition, cardiovascular/pulmonary complications, and abnormal bone metabolism were severe. SHPT patients had more hyperplastic parathyroid glands. The volume of each gland was smaller, and the time of ablation for a single parathyroid was shorter in the SHPT group, although there were no significant differences compared with patients in the PHPT group. Three patients in both groups had recurrent laryngeal nerve injuries and all recovered, except for one SHPT patient. By the end of follow-up, serum iPTH levels had decreased from 2400.26 ± 844.26 pg/mL to 429.39 ± 407.93 pg/mL (p < .01) in SHPT and from 297.73 ± 295.32 pg/mL to 72.22 ± 36.51 pg/mL in PHPT group (p < .01). Hypocalcemia was more common (p < .001) and serum iPTH levels were prone to rebound in SHPT patients after MWA.Conclusion: MWA can be reserved for those who had high surgical risks because of less invasiveness. Injuries of recurrent laryngeal nerves should be noticed. The health status, perioperative, and intraoperative procedures were more complicated and all parathyroids found by ultrasound should be ablated completely in SHPT patients.

99mTc-MIBI SPECT/CT imaging had high sensitivity in accurate localization of parathyroids before parathyroidectomy for patients with secondary hyperparathyroidism.

Purpose: Accurate preoperative parathyroid localization is important for successful parathyroidectomy (PTX). The aim of our study was to investigate whether SPECT/CT has enhanced effect in preoperative localization of parathyroids. Methods: In our retrospective cohort study, we evaluated the effects of technetium-99m methoxyisobutylisonitrile-single-photon emission computed tomography/computed tomography (99mTc-MIBI SPECT/CT) on preoperative parathyroid localization for 645 secondary hyperparathyroidism (SHPT) patients. Among them, 569 successful PTX patients were divided into group A (received 99mTc-MIBI scintigraphy, n = 175) and group B (received 99mTc-MIBI scintigraphy and SPECT/CT imaging, n = 394). Sensitivity, specificity, and consistency of two imaging methods in preoperative localization of parathyroids were compared. Results: Overall sensitivity and consistency were higher in group B, while there was no difference in specificity between the two groups. In group A, the sensitivity of 99mTc-MIBI was 50.00%, 77.11%, 61.76%, and 76.54% in the right upper gland (RU), right lower gland (RL), left upper gland (LU), and left lower gland (LL) subgroups, while the consistency was 52.00%, 76.57%, 61.71%, and 75.43%, respectively. In group B, the sensitivity of 99mTc-MIBI with SPECT/CT was 69.39%, 90.03%, 78.07%, and 84.27%, and the consistency was 69.54%, 88.32%, 78.43%, and 84.26%, respectively. The sensitivity and consistency in lower glands were higher than in upper glands in both groups. Sensitivity for eutopic parathyroid was higher in group B, while there was no difference for ectopic parathyroid. Conclusions: 99mTc-MIBI SPECT/CT can increase the sensitivity and consistency of preoperative localization of eutopic parathyroid glands, and it can accurately locate ectopic parathyroid without sensitivity improvement.

Relationship among Mortality of Patients with Acute Kidney Injury after Cardiac Surgery, Fluid Balance and Ultrafiltration of Renal Replacement Therapy: An Observational Study.

BACKGROUND/AIMS: The study aimed to investigate the relationship among mortality of patients with cardiac surgery-associated acute kidney injury (CSA-AKI), fluid balance, and ultrafiltration of renal replacement therapy (RRT). METHODS: From January 2009 to October 2015, hospitalized patients with CSA-AKI receiving continuous or prolonged intermittent RRT were screened. The effects of fluid balance and ultrafiltration of RRT on clinical outcome were analyzed. RESULTS: The 30-day mortality of all the 63 patients in the study was 58.6%. Compared with the death group, the survival group had a significantly lower fluid balance, larger ultrafiltration volume, and similar ultrafiltration rate during the first 3 days of RRT. Multivariate Cox regression analysis revealed that positive fluid balance during the first day of RRT, cardiac function of grade IV, and higher Sequential Organ Failure Assessment score were independent risk factors of 30-day mortality. CONCLUSION: Fluid balance was more relevant to short-term prognosis of CSA-AKI-RRT patients than ultrafiltration volume or ultrafiltration rate.

Effect of Cardiac Surgery-Associated Acute Kidney Injury on Long-Term Outcomes of Chinese Patients: A Historical Cohort Study.

BACKGROUND/AIMS: To evaluate the long-term outcomes of Chinese patients with cardiac surgery-associated acute kidney injury (CSA-AKI). METHODS: Patients who underwent cardiac surgery with a median 3-year follow-up were enrolled. The long-term survival rate and the incidence of chronic kidney disease (CKD) were recorded, and related risk factors were analyzed. RESULTS: Of all 1,363 patients, 457 (33.5%) developed CSA-AKI. The AKI patients had a lower 3-year survival rate (88.8 vs. 97.2%, respectively, p < 0.001) and a higher incidence of CKD stages 3-5 (9.9 vs. 2.3%, respectively, p < 0.001) than the non-AKI patients. Cox regression analysis showed that AKI, atrial fibrillation, chronic cardiac insufficiency, longer surgical duration, respiratory failure after surgery, and longer mechanical ventilation time were associated with long-term mortality, while AKI, older age, and lower baseline kidney function were associated with incident CKD stages 3-5. CONCLUSION: CSA-AKI increased the risk of 3-year mortality and incident CKD stages 3-5.

Parathyroidectomy Increases Heart Rate Variability and Leptin Levels in Patients with Stage 5 Chronic Kidney Disease.

BACKGROUND: In chronic kidney disease (CKD) patients, decreased heart rate variability (HRV) reflects impaired cardiac automatic nervous function and high risk of cardiovascular disease (CVD). Lower HRV in patients with severe secondary hyperparathyroidism (SHPT), a clinical manifestation of CKD-mineral and bone disorder (CKD-MBD), could be reversed by parathyroidectomy (PTX). It has been proved that leptin interacts with the autonomic nervous function. However, the associations between leptin and HRV in CKD patients and their longitudinal changes in SHPT patients after PTX are still unknown. METHODS: This was a cross-sectional study including 141 stage 5 CKD patients, and a prospective study in 36 severe SHPT patients with PTX. HRV was measured by Holter and serum leptin was measured by ELISA. Serum leptin levels were adjusted for body mass index (BMI) and transformed using natural logarithm (lnleptin/BMI). RESULTS: With a gradient of lnleptin/BMI across quartiles from Q1 to Q4 in CKD patients, HRV indices showed no differences among quartiles. Patients in Q1 group had higher mean 24 h heart rates, and lower ln(very low frequency) (lnVLF) than other quartiles, although there were no statistically significant difference. In multivariate stepwise regression, serum leptin/BMI was an independent predictor for low frequency/high frequency. HRV indices and lnleptin/BMI levels were increased in severe SHPT patients after PTX. Compared to other quartiles, SHPT patients in Q1 group had larger improvement of lnVLF after PTX. CONCLUSION: Circulating leptin levels may be a novel treatment target to reduce CVD risk in advanced CKD-MBD patients.

The relationship between AASI and arterial atherosclerosis in ESRD patients.

OBJECTIVE: To explore the relationship between ambulatory blood pressure and arterial atherosclerosis and provide simple and easy reference indicators for the prediction, prevention and prognosis of cardiovascular events in end-stage renal disease (ESRD) patients. METHOD: This prospective study consecutively collected clinical data of 114 ESRD hospitalized patients in the Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University during August 2012 to December 2012. The data included laboratory data, the ambulatory blood pressure monitoring (ABPM), carotid ultrasound, two-dimensional echocardiography and the prognosis scores of the death risk. RESULTS: (1) A series of ABPM parameters were closely associated with atherosclerosis (p ≤ 0.05). Ambulatory Arterial Stiffness Index (AASI) was the most representative parameter of ABPM and also the best indicator for atherosclerosis (logistic regression analysis, p = 0.005). (2) AASI was a comprehensive index of atherosclerosis (p < 0.001), which was associated with the increase of left ventricular diameter (p = 0.028) and the risk of death (p < 0.001). The independent risk factors of AASI were the growth of the age (p < 0.001), elevated serum fibrinogen (p = 0.009) and reduced serum albumin (p = 0.022). CONCLUSION: AASI, as the representative of ABPM parameters, related well to atherosclerosis, which implied a broader application of ABPM in ESRD patients.

Prognostic factors in continuous hemofiltration therapy for patients with cardiorenal syndrome.

AIMS: The aims of this study were to investigate the efficacy and identify the prognostic factors of continuous hemofiltration in patients with cardiorenal syndrome (CRS) and, finally, to optimally select patients who could benefit more from this therapy. METHODS: A total of 59 patients with CRS type 1 or type 2 treated with continuous hemofiltration were enrolled. We collected their clinical data and divided them into 2 groups according to their survival or death during hospitalization to conduct a retrospective analysis on factors affecting mortality. RESULTS: The following items were significantly different between the survival (n = 30) and death (n = 29) groups: serum creatinine, serum total bilirubin, direct bilirubin, white blood cells, hemoglobin, hematocrit, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, systolic blood pressure and mean arterial pressure before hemofiltration, and average dehydration volume during the hemofiltration process. Leukocytosis was a risk factor for death (OR 1.242, 95% CI 1.242-1.480), and elevated sCr was not a key negative factor in the prognosis of CRS (OR 0.994, 95% CI 0.989-1.000). CONCLUSIONS: Cardiac function before hemofiltration and the amount of dehydration during the hemofiltration process both affected the prognosis. Infection and fluid overload condition at the beginning of hemofiltration were independently associated with mortality during hospitalization.

Clinical characteristics and outcome of double-seropositive patients with anti-glomerular basement membrane antibodies and anti-neutrophil cytoplasmic antibodies.

OBJECTIVE: To explore the clinical characteristics of double-seropositive patients (DPPs) with anti-glomerular basement membrane (Anti-GBM) antibodies and anti-neutrophil cytoplasmic antibodies (ANCA). METHODS: We collected patients with both ANCA and anti-GBM positive glomerulonephritis who were hospitalized in the Department of Nephrology at the First Affiliated Hospital of Nanjing Medical University from January 2010 to August 2022. Retrospective analysis of the baseline clinical characteristics of patients and follow-up to explore relevant factors affecting renal and patient survival. RESULTS: A total of 386 patients, including 69 ANCA negative anti-GBM glomerulonephritis patients, 296 anti-GBM negative ANCA associated vasculitis (AAV) patients, and 21 DPPs were enrolled in this study. Among the 21 DPPs aged 68.0 years (59.5, 74.0), there were 11 males and 10 females. The median serum creatinine at diagnosis was 629.0 (343.85, 788.75) µmol/L, and the median eGFR (CKD-EPI) was 7.58 (4.74, 13.77) mL/min. Fifteen cases (71.4 %) underwent initial RRT. After a follow-up of 40.0 (11.0, 73.0) months, 13 out of 21 DPPs (61.9 %) received maintenance RRT, while 49 out of 69 (71.0 %) ANCA negative anti-GBM-GN patients and 124 out of 296 (41.9 %) anti-GBM negative AAV patients received maintenance RRT (P < 0.001). Kaplan-Meier survival analysis showed that DPPs and ANCA negative anti-GBM-GN patients were more likely to progress to ESRD than anti-GBM negative AAV patients (P = 0.001). Among the 21 patients with DPPs, renal survival was significantly better in patients with better initial renal function, including those who did not receive initial RRT (P = 0.003), with lower serum creatinine levels (Cr < 629.0 µmol/L, P = 0.004) and higher eGFR levels (eGFR ≥ 7.60 ml/min, P = 0.005) than those with poor initial renal function. At the end of follow-up, 14 out of 21 DPPs (66.7 %) survived. Survival analysis showed no significant difference among patients in DPPs group, ANCA negative anti-GBM-GN group, and anti-GBM negative AAV group. CONCLUSIONS: DPPs and ANCA negative anti-GBM-GN patients were more likely to progress to ESRD than anti-GBM negative AAV patients. In DPPs, the poor renal function at diagnosis might be a risk factor associated with poor renal survival.

Role of TGF-beta1 in bone matrix production in vascular smooth muscle cells induced by a high-phosphate environment.

AIMS: We demonstrated a relationship between transforming growth factor-beta(1) (TGF-beta(1)) and production of bone matrix in vascular smooth muscle cells (VSMCs) induced by a high-phosphate environment. METHODS: Rat VSMCs were incubated in a high-phosphate (2.5 or 3.5 mM) or TGF-beta(1) (2 or 5 ng/ml) environment. TGF-beta(1) monoclonal neutralization antibody (50 microg/ml) was added to inhibit the TGF-beta(1) signal in high-phosphate medium. Production of TGF-beta(1) was analyzed by Western blot and real-time PCR. Core binding factor a1 (Cbfa1), osteopontin (OP), collagen type I (Col I) and osteocalcin (OC) was investigated by Western blot and immunofluorescence staining. Mineral deposition was assessed by von Kossa staining and o-cresolphthalein complexone method. RESULTS: VSMCs transformation induced by high phosphate occurs via an autocrine loop of TGF-beta(1). First, high phosphate stimulated the production of TGF-beta(1) in VSMCs. Second, TGF-beta(1) could induce increased expression of osteoblast-specific transcription factor Cbfa1 and osteogenic molecule in VSMCs. Third, the TGF-beta(1) neutralization antibody largely attenuated the upregulation of Cbfa1 and bone matrix in high-phosphate-stimulated cells. However, neutralization of TGF-beta(1) could not inhibit high-phosphate-induced VSMCs calcification, indicating that TGF-beta(1) was not necessary for the deposition of calcium. CONCLUSION: TGF-beta(1) plays a crucial role in bone matrix production but not calcium deposition in VSMCs induced by a high-phosphate environment, and the blockade of TGF-beta(1) signaling may thus be a therapeutic strategy for use with vascular disease in a high-phosphate environment.

Outcome Predictors of Biopsy-Proven Myeloperoxidase-Anti-Neutrophil Cytoplasmic Antibody-Associated Glomerulonephritis.

Objective: To determine the prognostic values of histopathologic classification of myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis and other clinical and laboratory features at the time of presentation on renal and patient survival associated with myeloperoxidase-ANCA-associated glomerulonephritis (MPO-ANCA-GN). Methods: A total of 112 patients diagnosed with MPO-ANCA-GN from October 2005 to December 2018 were enrolled. The baseline clinical characteristics, renal histopathological data, and risk factors predictive of renal and patient survival were retrospectively analyzed. Results: All 112 patients underwent renal biopsy. Disease in 32 patients was classified as focal, 26 as mixed, 29 as crescentic, and 25 as sclerotic. Over a median follow-up period of 41.5 months, there were 44 patients dialysis-dependent. The renal survival rate was significantly higher in the focal group than the other groups (p < 0.001) and significantly lower in the sclerotic group (p < 0.05). In addition, disease histopathologically classified as sclerotic (p = 0.044), high serum creatinine level (≥320 µmol/L, p < 0.001), low albumin (<30 g/L, p = 0.024) and hemoglobin level (<90 g/L, p = 0.044) were associated with a greater risk of ESRD. After follow-up, 70 (62.5%) of 112 patients survived. Old age (≥60 years, p = 0.018) and low serum albumin (<30 g/L, p = 0.006) was significant risk factor for patient survival. Conclusion: Among patients with MPO-ANCA-GN, those with poor renal function, disease histopathologically classified as sclerotic, and lower albumin and hemoglobin levels were risk factors for ESRD, while older age and low serum albumin level were associated with a greater risk for all-cause mortality.

Bone metabolism markers and hungry bone syndrome after parathyroidectomy in dialysis patients with secondary hyperparathyroidism.

OBJECTIVE: To explore the short-term variation in bone metabolic markers and the characteristics of hungry bone syndrome (HBS) after parathyroidectomy (PTX) with forearm autotransplantation in uremic patients with secondary hyperparathyroidism (SHPT) and to provide a basis for the pathogenesis, diagnosis and treatment of metabolic bone disease in SHPT. METHODS: A total of 115 patients with SHPT receiving PTX from July 2015 to December 2017, hospitalized at the First Affiliated Hospital of Nanjing Medical University, were enrolled in our study. We retrospectively analyzed the baseline clinical data, the levels of bone metabolism markers before and on the third day after PTX, and the risk factors predicting HBS. RESULTS: Preoperative baseline data showed that the levels of bone metabolic markers such as bone metabolism-regulating hormones: iPTH, calcitonin (CT); bone formation markers: phosphatase (ALP), osteocalcin (OC); bone resorption markers: type I collagen cross-linked N-telopeptides (NTX), type I collagen cross-linked C-telopeptides (CTX), tartrate-resistant acid phosphatase 5b (TRAP-5b) were all increased compared to normal levels. The levels of postoperative serum iPTH, CT, CTX and TRAP-5b decreased significantly compared to preoperative levels, while the levels of OC and ALP increased significantly. Of the 115 patients, 101 (87.8%) developed HBS after PTX. High preoperative serum ALP and low preoperative serum calcium level independently predicted the occurrence of HBS. Younger preoperative age, high preoperative serum ALP and iPTH level independently predicted the severity of HBS. CONCLUSIONS: In severe SHPT, both bone formation and resorption were active, which suggested the presence of high-turnover bone diseases characterized by up-regulation of osteoclasts-osteoblasts functionally coupling activation in the patients. PTX could promote osteoblast activity and reduce osteoclast activity. HBS was common after PTX. Preoperative higher serum ALP and lower calcium were independent predictors of the occurrence of HBS. Younger patients with higher preoperative ALP and PTH may need to closely monitor serum calcium levels and intensive calcium supplementation after PTX.

Renal thrombotic microangiopathies induced by severe hypertension.

Renal thrombotic microangiopathy (TMA) is an uncommon vascular complication of severe hypertension. Until now, its clinical-pathological characteristics and renal survival have been unclear. Twenty-one patients with biopsy-proven renal TMA and with severe or malignant hypertension were retrospectively studied. All the patients exhibited severe hypertension, with systolic blood pressure at 200-280 mmHg and diastolic pressure at 110-180 mmHg. No patients had hemorrhagic manifestations. Elevated lactate dehydrogenase and thrombocytopenia were found in 6 and 5 patients, respectively. Significant proteinuria (>3 g/day) was present in 2 patients and microscopic hematuria in 18 patients. All patients presented with renal insufficiency (creatinine 3.1+/-2.1 mg/dL). The level of von Willebrand factor:antigen (vWF:Ag) in patients was not significantly higher than that in the healthy subjects, while the ADAMTS13 (a disintegrin and metalloprotease, with thrombospondin-1-like domains) activity was not significantly lower than that in the healthy subjects. Renal histology showed a TMA involving preglomerular arterioles and/or interlobular arteries characterized by fibrin deposits and vascular wall sclerosis. Fibrin glomerular microthrombi were not observed in these patients. Four patients required hemodialysis upon admission for severe acute renal failure. On follow-up, 3 patients had recovered normal renal function and 14 had mild renal insufficiency (creatinine 1.8+/-0.3 mg/dL), while 4 patients still required persistent hemodialysis. In conclusion, compared with patients having hemolytic uremic syndrome/thrombocytopenic purpura, our patients showed a low incidence of thrombocytopenia and better renal outcome.

Radial artery calcification in end-stage renal disease patients is associated with deposition of osteopontin and diminished expression of alpha-smooth muscle actin.

AIM: Vascular access is the lifeline of haemodialysis patients and radial-cephalic fistula is the preferred type of access. We investigated vascular calcification in uraemia radial arteries and compared it with clinical parameters. METHODS: Artery specimens from 30 end-stage renal disease patients were collected, examined calcification by von Kossa and Alizarin red staining. Expression of alpha-smooth muscle actin (alpha-SMA) and the main component of bone matrix, osteopontin (OP) were detected by immunohistochemistry. RESULTS: In uraemia vessels, calcification was mainly located in the medial layer. Nineteen (63.33%) patients had no evidence of calcification, six (20%) had mild/moderate calcification and five (16.66%) had severe calcification. Upregulation of OP and diminished expression of alpha-SMA occurred in the medial layer, especially in the area of severe calcification. The calcification score, decreased expression of alpha-SMA and upregulation of OP were positively correlated with older age, serum calcium, serum phosphorus and calcium x phosphorus product (P < 0.01). CONCLUSION: Vascular calcification in uraemia radial arteries is mainly located in the media layer. The risk factors appear to be older age, an elevated serum level of phosphorus, calcium and calcium x phosphorus product.

Hypocalcemia-based prediction of hungry bone syndrome after parathyroidectomy in hemodialysis patients with refractory secondary hyperparathyroidism.

OBJECTIVE: This study was performed to explore the risk factors for hungry bone syndrome (HBS) and establish prediction equations for calcium supplementation after parathyroidectomy in hemodialysis patients with secondary hyperparathyroidism. METHODS: We retrospectively analyzed data from 252 hemodialysis patients undergoing successful total parathyroidectomy with autotransplantation. HBS was defined according to a minimum postoperative serum corrected calcium (PcCa) concentration of <2.0 mmol/L. Independent predictors of HBS were analyzed, and prediction equations for HBS were derived accordingly. Results The incidence of HBS was 71.4%. The serum corrected calcium and preoperative serum alkaline phosphatase (ALP) concentrations were independent predictors of HBS. The preoperative serum ALP, intact parathyroid hormone (iPTH), and hemoglobin concentrations were independent factors influencing the average descending velocity of the PcCa concentration before calcium supplementation (PcCa-V), intravenous calcium supplement holding time (IVCa-T), and intravenous calcium supplement dosage (IVCa), while the serum ALP and iPTH concentrations were independent predictors of the oral calcium supplement dosage (OCa). Four prediction equations for PcCa-V, IVCa-T, IVCa, and OCa were established. CONCLUSIONS: Establishment of prediction equations for HBS may contribute to a new individualized therapy for patients with HBS.

Effects of parathyroidectomy on blood bone markers and heart rate variability in patients with stage 5 chronic kidney disease.

PURPOSE: Decreased heart rate variability (HRV) is closely related to abnormal cardiac autonomic nervous function, especially sympathetic hyperactivity, which intensifies the risk of cardiovascular events and sudden death. HRV parameters are lower in chronic kidney disease (CKD) and parathyroidectomy (PTX) can improve these abnormalities in severe secondary hyperparathyroidism (SHPT) patients. However, few studies have evaluated correlations between circulating bone markers and HRV in CKD patients. METHODS: We conducted a cross-sectional study including 134 stage 5 CKD patients with 100 controls and a prospective study of 29 PTX patients with follow-up. Circulating bone biomarkers included: (1) intact parathyroid hormone (iPTH) as bone remodeling regulator; (2) bone-specific alkaline phosphatase (BAP), representing bone formation; (3) tartrate-resistant acid phosphatase 5b (TRACP-5b), indicating bone resorption; and (4) bone-derived hormone, fibroblast growth factor 23 (FGF23). RESULTS: Stage 5 CKD patients had higher circulating iPTH, BAP, TRACP-5b, and FGF23 than controls and these bone markers were significantly elevated in SHPT patients. Baseline iPTH, BAP, and lnFGF23 were independently associated with HRV in CKD patients. After PTX with a follow-up (median interval: 6.7 months), high blood iPTH, BAP, TRACP-5b, FGF23, and attenuated HRV were ameliorated. Furthermore, improved HRV indices were associated with reduced iPTH, BAP, TRACP-5b, and FGF23. CONCLUSIONS: Circulating bone markers are correlated with HRV in CKD 5 patients and PTX can improve decreased HRV, which are associated with corrected bone markers in severe SHPT patients. Thus, we propose that PTH increases sympathetic tone and both high circulating PTH levels and sympathetic hyperactivity increase bone turnover, and that the products of bone turnover influence HRV.