Prognostic Assessment of Histopathologic Lesions in Patients with Community-Acquired Acute Kidney Injury with Biopsy-Proven Acute Tubular Necrosis.

BACKGROUND: Community-acquired acute kidney injury (CA-AKI) was more likely to be comorbid with underlying kidney histopathological lesions in addition to acute tubular necrosis (ATN). Thus, we tried to clarify the histological determinants that could influence the prognosis and recovery of CA-AKI patients with biopsy-proven ATN. METHODS: Adult patients with CA-AKI with biopsy-proven ATN who underwent renal biopsy at Shanghai Changzheng Hospital from January 1, 2010, to December 31, 2018, were included and followed up for 5 years. The impacts of histopathological lesions on short-term and long-term renal dysfunction were also analysed. RESULTS: Multivariate analysis revealed that ATNs, crescents, and decrease of arteriole lumens increased short-term dialysis requirements. The severity of ATN was closely associated with renal survival. According to the Kaplan-Meier analysis, the severity of ATN was significantly associated with short-term dialysis needs and long-term development of end-stage kidney disease (ESKD) during follow-up. Crescent and decrease of arteriole lumens are significantly associated with progression to ESKD and exert synergistic effects with ATN. For patients who did not progress to dialysis, tubular atrophic/interstitial fibrosis and endocapillary lesions were more relevant to partial recovery of renal function after CA-AKI at the three-month follow-up and increased the risk of chronic kidney disease (CKD) stage 3-5 at the five-year follow-up. According to our correlation analysis, endocapillary lesions and crescents were positively correlated with ATN. CONCLUSIONS: Histopathologic lesions, apart from tubular necrosis, contributed to the detrimental short-term and long-term renal prognosis of CA-AKI patients with ATN; concomitant histopathologic lesions exerted a combined impact on renal survival together with ATN in CA-AKI patients.

A Nomogram to Identify Hyperkalemia Risk in Patients with Advanced CKD.

Background: Hyperkalemia is a common and life-threatening complication of CKD. We aimed to develop and validate a nomogram that could identify the risk of hyperkalemia (≥5.5 mmol/L) in patients with CKD. Methods: A retrospective cohort study was performed in adult patients with predialysis advanced CKD (stages ≥3) in 2020-2021 for the outcome of hyperkalemia within 6 months. The training set was used to identify risk factors of hyperkalemia. Then a nomogram was developed by multivariable logistic regression analysis. C-statistics, calibration curves, and decision curve analysis (DCA) were used, and the model was validated in the internal and two external validation sets. Results: In total, 847 patients with advanced CKD were included. In 6 months, 28% of patients had hyperkalemia (234 out of 847). Independent risk factors were: age ≥75 years, higher CKD stages, previous event of serum potassium ≥5.0 mmol/L within 3 months, and comorbidities with heart failure, diabetes, or metabolic acidosis. Then the nomogram on the basis of the risk factors adding the use of renin-angiotensin-aldosterone system inhibitors was constructed. The C-statistic of the model was 0.76 (95% CI, 0.70 to 0.78), and was stable in both the internal validation set (0.73; 95% CI, 0.63 to 0.82) and external validation sets (0.88; 95% CI, 0.84 to 0.95 and 0.82; 95% CI, 0.72 to 0.92). Calibration curves and DCA analysis both found good performances of the nomogram. Conclusion: A feasible nomogram and online calculator were developed and validated to evaluate the risk of hyperkalemia within 6 months in patients with advanced CKD. Patients with CKD and a high risk of hyperkalemia may benefit from intensive monitoring and early triage.

PKD2 gene variants in Chinese patients with autosomal dominant polycystic kidney disease.

PKD2 gene variants account for 4.5% to 20% of patients with autosomal dominant polycystic kidney disease (ADPKD). Little is known about the clinical characteristics of PKD2 variants in Chinese patients with ADPKD. Herein, we performed a comprehensive search for variants of PKD2 gene in 44 Chinese ADPKD pedigrees and a total of 37 variants were identified. Of these 37 variants, 18 were nonsense variants, 10 frameshift variants, 4 missense variants, and 5 splice site variants. 11/37 variants were detected for the first time. The median age at diagnosis was 30.5 years, and positive family history was detected in 77.27% patients, liver cysts in 68.18%, hypertension in 45.45%, nephrolithiasis in 31.82%, macro-hematuria in 22.73%, and proteinuria in 13.63%. The level of estimated glomerular filtration rate in 8/39 patients were blow 60 ml/min/1.73m2 . 11/17 patients were classified as rapid progression by Mayo Clinic classification. The end stage renal disease (ESRD) events were reported in 9/22 pedigrees, and the presence of nephrolithiasis and macro-hematuria were significantly associated with ESRD in the pedigrees with PKD2 variants. The identified variants and clinical features will facilitate the early diagnosis and prognosis prediction in Chinese ADPKD patients with PKD2 variants.

High hsa_circ_0020123 expression indicates poor progression to non-small cell lung cancer by regulating the miR-495/HOXC9 axis.

Circular RNAs (circRNAs) belong to non-protein-coding RNAs that regulate different pathophysiological procedures. Upregulation of hsa_circ_0020123 is found in non-small cell lung cancer (NSCLC); however, its activity and functions are not clear. In this study, the results showed that hsa_circ_0020123 expression increased in both tumor tissues and NSCLC cells. A higher hsa_circ_0020123 expression also led to poor prognoses among NSCLC patients assayed via FISH. The data of FISH also confirmed that hsa_circ_0020123 primarily had a cytoplasmic location. Hsa_circ_0020123 knockdown caused a significant decrease in nude mouse xenograft growth. Bioinformatics analyses and dual luciferase reporter assays confirmed that hsa_circ_0020123 was an miR-495 sponge and that the HOXC9 gene was a miR-495 target. The miR-495 downregulation reversed cell migration and proliferation inhibition induced by hsa_circ_0020123 silencing in vitro. HOXC9 overexpression reversed miR-495-induced inhibition of cell migration and proliferation. The dual luciferase reporter assay demonstrated that hsa_circ_0020123 interacted with miR-495 by binding to the HOXC9 3'-UTR to suppresses post-transcriptional HOXC9 expression. Taken together, our study found that hsa_circ_0020123 functioned like a tumor promoter via a novel hsa_circ_0020123/miR-495/HOXC9 axis, highlighting its possibility as a new NSCLC therapeutic target.

The fertility willingness and acceptability of preimplantation genetic testing in Chinese patients with autosomal dominant polycystic kidney disease.

BACKGROUND: With the development and progression of genetic technology, preimplantation genetic testing (PGT) has made it possible to block the inheritance of autosomal dominant polycystic kidney disease (ADPKD) as early as possible. However, we need to know the patients' fertility intentions and their acceptance of PGT. METHODS: A questionnaire survey was conducted to collect data on the basic demographic data, quality of life, social support, fertility willingness, and level of understanding of genetic testing for blocking the inheritance of ADPKD among patients aged 18-45 years in seven hospitals from January 2018 to December 2018. After verification, statistics were calculated. RESULTS: A total of 260 patients with ADPKD were interviewed, including 137males (52.7%) and 123 females (47.3%). The overall fertility willingness rate was low (n = 117, 45.0%). The proportion of married patients aged 25-34 years that were at the optimal reproductive age but did not yet have children was relatively high (n = 77, 67.0%). The fertility intentions of ADPKD patients were significantly influenced by age (OR: 0.101, 95% CI 0.045-0.225, P < 0.001) and education level (OR: 2.134, 95% CI 1.162-3.917, P = 0.014). Among patients who are willing to have children, 207 (79.6%) of them would choose PGT technology. Among those who were not sure whether they would choose PGT technology, the first major concern was technical safety (49.2%). CONCLUSIONS: The reproductive desire of childbearing ADPKD patients in China was low. Strengthening the health education of ADPKD genetic knowledge and reducing the cost of related technologies may improve the fertility intentions and reduce the barriers to acceptance of PGT.

Detection of exosomal tyrosine receptor kinase B as a potential biomarker in ovarian cancer.

Ovarian cancer (OC) is a lethal disease diagnosed at advanced stages due to the lack of specific biomarkers. Tyrosine receptor kinase B (TrkB), which has recently been found to be related to OC progression, represents a promising potential biomarker for OC diagnosis and prognosis. The discovery of circulating exosomes as biomarkers for various diseases led us to explore exosomal TrkB in OC. Our previous study proved that the expression of TrkB was elevated in OC tissues. In this study, we focused on the detection of exosomal TrkB in OC. Exosomes were first gathered from three different OC cell lines' conditioned medium, serum samples of patients with OC as well as xenograft mice serum by serial centrifugation method. Then, we identified exosomes by transmission electron microscopy, NanoSight analysis, and expression of typical exosomal protein markers. The existence of TrkB in exosomes was measured by Western blot analysis, and the expression was detected by enzyme-linked immunosorbent assay. In this study, we demonstrated that exosomes could derive from OC cell lines, serum from OC xenograft nude mice, and clinical patients. Our study shows that serum exosomal TrkB may be considered a minimally invasive biomarker for OC.

Novel Mutations in the PKD1 and PKD2 Genes of Chinese Patients with Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND/AIMS: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder with mutations in PKD1 or PKD2. This study aimed to identify novel PKD1 and PKD2 mutations in Chinese patients with ADPKD. METHODS: Mutational analyses of both PKD genes were performed in 120 Chinese families with inherited ADPKD using long-range PCR and targeted next-generation sequencing approaches. Sanger sequencing was performed to check the positive mutations, while multiplex ligation-dependent probe amplification was adopted to examine those without mutations for the presence of large deletions. RESULTS: A total of 93 mutations in PKD1 and PKD2 were identified in 98 Chinese families with ADPKD inheritance and the detection rate was 81.7% (98/120). The mutation rates of PKD1 and PKD2 were 91.4% (85/93) and 8.6% (85/93), respectively. Among the 93 mutations, 59.1% (55/93) were reported for the first time. A total of 65 mutations (26 nonsense, 33 frameshift, 2 large deletion, and 4 typical splicing mutations) were identified as definite pathogenic mutations. The remaining 28 mutations (21 missense, 3 in-frame deletion, and 4 atypical splicing mutations) were determined as probable pathogenic mutations. In addition, 9 de novo mutations were found by pedigree analysis. Correlation analysis between genotype and phenotype revealed that patients with PKD1 mutations or truncating mutations exhibited the most severe clinical outcome. CONCLUSION: The newly identified sites for known mutations will facilitate the early diagnosis and prediction of prognosis in patients with ADPKD, and provide fundamental genetic information for clinical intervention to prevent the inheritance of this disease in affected families.

The Determination of Nitrate and Nitrite in Human Urine and Blood by High-Performance Liquid Chromatography and Cloud-Point Extraction.

A simple efficient and practical separation/preconcentration coupled with HPLC method for the determination nitrate and low concentrations of nitrite in human urine and blood was investigated. The method is based on precolumn derivatization using the Griess reaction and cloud-point extraction (CPE) of nitrite anion and direct determination of nitrate using its UV absorbance by ion-pair HPLC. The chromatographic process with detection at two wavelengths (510 and 220 nm) allows the determination of nitrite and nitrate. Decolorization and protein precipitation of urine and blood was applied to overcome the interference of matrix and enhance the sensitivity. The method was validated for linearity, accuracy and precision. Under the optimum conditions, the linear range of nitrite from 10 to 1,000 ng/mL and nitrate from 0.1 to 10 µg/mL. Product recoveries ranged from 92.4 to 99.9%. The limits of detection were 1 ng/mL and 0.1 µg/mL for nitrite and nitrate, respectively. Therefore, the technique was simple and reliable, with potential application in biological sample analysis of nitrate and nitrite.

Development of a cloud point extraction and spectrophotometry-based microplate method for the determination of nitrite in human urine and blood.

A novel and simple method for the sensitive determination of trace amounts of nitrite in human urine and blood has been developed by combination of cloud point extraction (CPE) and microplate assay. The method is based on the Griess reaction and the reaction product is extracted into nonionic surfactant Triton-X114 using CPE technique. In this study, decolorization treatment of urine and blood was applied to overcome the interference of matrix and enhance the sensitivity of nitrite detection. Multi-sample can be simultaneously detected thanks to a 96-well microplate technique. The effects of different operating parameters such as type of decolorizing agent, concentration of surfactant (Triton X-114), addition of (NH4)2SO4, extraction temperature and time, interfering elements were studied and optimum conditions were obtained. Under the optimum conditions, a linear calibration graph was obtained in the range of 10-400 ng mL(-1) of nitrite with limit of detection (LOD) of 2.5 ng mL(-1). The relative standard deviation (RSD) for determination of 100 ng mL(-1) of nitrite was 2.80%. The proposed method was successfully applied for the determination of nitrite in the urine and blood samples with recoveries of 92.6-101.2%.

[Daytime hypercapnia in patients with obstructive sleep apnea hypopnea syndrome].

OBJECTIVES: To evaluate the incidence and factors related to daytime CO2 retention (PaCO2 ≥ 45 mm Hg, 1 mm Hg = 0.133 kPa) in Chinese patients with obstructive sleep apnea hypopnea syndrome. METHODS: 1441 patients with OSAHS had daytime arterial blood gas analysis were recruited from 2007 to 2009 in Peking University People's Hospital. 145 patients underwent pulmonary function test and had FEV1/FVC ratio over 70% were under further analysis. Sex, age, BMI, pulmonary function, polysomnography (PSG) and blood gas analysis results were recorded. Linear regression analysis was used to evaluate the relationship between PaCO2 levels and related parameters. Comparison was done between hypercanpnic and eucapnic patients. RESULTS: Daytime hypercapnia occurred in 25.2% of the 1441 patients with OSAHS, and 26.9% in the 145 OSAHS patients who had lung function test and with FEV1/FVC ratio over 70%. PaCO2 was correlated with BMI, PaO2 and the severity of nocturnal hypoxemia as reflected by the mean SpO2 and SIT90. This was also confirmed by the comparison between the hypercapnic and eucapnic patients. CONCLUSIONS: Hypercapnia occurs in a large part of patients with OSAHS and normal FEV1/FVC. BMI, nocturnal hypoxemia and daytime PaO2 level are all contributed to the development of daytime CO2 retention in OSAHS.

[Effect of acute hypoxia and hypercapnia on arterial stiffness and blood pressure in patients with obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To investigate the effect of acute hypoxia and/or hypercapnia on cardio-ankle vascular index (CAVI) and blood pressure (BP) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHOD: CAVI and blood pressure were measured before and after isocapnic hypoxic, hyperoxia hypercapnic, and hypoxic and hypercapnic challenge in 28 non-hypertensive patients with OSAHS (AHI > 10/h) and 26 healthy controls (AHI < 5/h), respectively. They were matched for age and sex. Hypoxia and hypercapnia were induced by re-breathing technique. RESULTS: The 2 groups had no differences in regard to systolic (SBP) and diastolic BP(DBP) and CAVI. After hypercapnic challenge, SBP increased significantly in both groups. CAVI decreased significantly in controls, but not in OSAHS. Hypoxia induced significant increase of CAVI, but not in OSAHS. SBP and DBP maintained to the pre-challenge levels in both group. Hypercapnia and hypoxia together caused increase of SBP in both groups, and CAVI increased significantly in controls, but not in OSAHS. CONCLUSIONS: Acute hypoxia and hypercapnia exposure caused change of arterial stiffness and BP in both control and patients with sleep apnea hypopnea syndrome. However, CAVI responses to hypoxic and/or hypercapnic challenge were blunted in patients with OSAHS.

[Effects of short-term continuous positive airway pressure treatment on arterial stiffness in patients with obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To investigate the effect of short-term continuous positive airway pressure (CPAP) treatment on the arterial stiffness in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: Cardio ankle vascular index (CAVI) and blood pressure (BP) were measured before and after sleep in 60 non-hypertensive patients with OSAHS and gender and 60 age-matched healthy controls. CPAP was administrated in 22 of the 60 OSAHS patients. And on the first and third days of the CPAP treatment CAVI and BP were measured in the morning, i. e., after sleep. RESULTS: In the morning, the CAVI of the OSAHS patients was 8.0 +/- 1.2 m/s, significantly higher than that before sleep (7.3 +/- 1.0, P = 0.000), the diastolic BP (DBP) was (86 +/- 12) mm Hg, significantly higher than that before sleep (83 +/- 13 mmHg, P = 0.001), and the mean BP (MBP) was (101 +/- 12) mm Hg, significantly higher than that before sleep (98 +/- 14, P = 0.00116). However, there were no significant differences in these parameters among the controls The systolic BP (SBP) of the OSAHS patients did not changed significantly after sleep, however, there was a tendency to decrease in the controls [(123 +/- 14) vs (121 +/- 13) mm Hg, P = 0.074). After the first night treatment, the CAVI, SBP, DBP, and mean BP of the 22 severe OSAHS patients decreased significantly (all P < 0.05), and after three nights treatment, only the CAVI showed further significant decrease (P < 0.05). CONCLUSION: Sleep induces increase of artery stiffness in OSAHS patients, but not in the normal controls. Short-term CPAP may decrease CAVI without affecting the blood pressures. Early atherosclerosis in the patients with OSAHS may be reversed by CPAP therapy.

[Respiration control dysfunction and the relationship to sleep-disordered breathing in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To analyze the polysomnographic (PSG) features of sleep apnea hypopnea syndrome (SAHS) in patients with chronic obstructive pulmonary disease (COPD), and to define the association between SAHS and respiratory control disorder. METHODS: Three hundred patients with stable COPD were screened for SAHS using questionnaire, Epworth sleep scale (ESS) and home pulse oximeter testing. Those with ESS > or = 10 or oxygen desaturation over 3% more than 5 times per hour sleep were under further PSG testing. The PSG features were compared between COPD patients with apnea hypopnea index (AHI) > 10 and 118 SAHS patients with normal lung function. The two groups were matched for age, body mass index (BMI) and AHI. Among them 22 with COPD and AHI > or = 10 were tested for the chemo-responsiveness to isocapnic hypoxia and hypercapnia. RESULTS: Among the 300 patients with stable COPD, 79 had AHI over 10, meeting the diagnostic criteria of overlap syndrome (OS). Analysis of the polysomnography found that 32 cases (40%) with OS had more hypoventilation lasting over 1 min during sleep. Compared to patients with SAHS only, OS patients had higher percentage of hypopnea index over AHI [(69 +/- 30)% vs (52 +/- 31)%] and a higher percentage of total hypopnea time over total time of sleep apnea and hypopnea [(15 +/- 12)% vs (12 +/- 10)%]. OS patients also had lower hypoxic [(-0.11 +/- 0.05) vs (-0.35 +/- 0.24) L.min(-1).%(-1)] and hypercapnic responses [(1.1 +/- 0.8) vs (1.6 +/- 0.8) L.min(-1).mm Hg(-1) (1 mm Hg = 0.133 kPa)]. CONCLUSION: Patients with both COPD and SAHS had more episodes of hypopnea and hypoventilation during sleep, and had depressed chemo-responsiveness to hypoxia during wakefulness.

[Effect of noninvasive ventilation on chemoresponsiveness in patients with sleep apnea and chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the effect of noninvasive ventilation on respiratory control in patients with chronic obstructive pulmonary disease (COPD) combined with sleep a apnea-hypopnea syndrome (SAHS)-overlap syndrome (OS). METHODS: Ten body mass index, apnea-hypopnea index, and age-matched OSAHS patients, 5 being hypercapnic (PaCO(2) > 45 mm Hg) OSAHS patients with normal FEV(1)/FVC, and 5 being OSAHS patients with COPD and the mean FEV(1)/FVC of 59% +/- 6% underwent bi-level positive airway pressure (BiPAP) treatment. Hypoxic responses, including the ratio of the change in minute ventilation (DeltaVE) to the change in arterial oxygen saturation (DeltaSaO(2)), and hypercapnic responses (DeltaVE/DeltaPaCO(2) ratio) were tested during wakefulness before treatment and 6 weeks after the treatment. RESULTS: Before treatment, the DeltaVE/DeltaSaO(2) ratios of the OS and OSAHS patients were (-0.023 +/- 0.049) L.min(-1).%(-1) and (-0.16 +/- 0.06) L.min(-1).%(-1) respectively, both lower than the laboratory normal value [(-0.35 +/- 0.21) L.min(-1).%(-1)]. The DeltaVE/DeltaPaCO(2) ratio of the OS patients was (0.54 +/- 0.16) L.mm Hg(-1), significantly lower than the normal value [(1.26 +/- 0.54) L.mm.Hg(-1), P < 0.05]. After receiving 6 weeks of noninvasive ventilation treatment, the hypoxic response of OSAHS patients were (-0.16 +/- 0.06) L.min(-1).%(-1), significantly higher than that before treatment [(-0.36 +/- 0.14) L.min(-1).%(-1)], and hypercapnic response of the OSAHS patients was (1.30 +/- 0.62) L.min(-1).mm Hg(-1), significantly lower than that before treatment [(1.78 +/- 0.93) L.min(-1).mm Hg(-1)], both bring within the normal ranges. In the patients with OS, the hypercapnic response was unchanged [(0.54 +/- 0.16) vs (0.51 +/- 0.23) L.min(-1).mm Hg(-1)], and the hypoxic responses increased significantly but still remained at a very low level [(-0.023 +/- 0.049) vs (-0.09 +/- 0.007) L.min(-1).%(-1)] after treatment. CONCLUSION: Hypercapnic and hypoxic responses in patients with OS and in patients with OSAHS respond differently after pressure support ventilation. This indicates that depressed chemoresponsiveness in patients with OS may not be only a response to sleep-disordered breathing.

[Changes of sleep architecture in patients with narcolepsy].

OBJECTIVE: To investigate the sleep architectures of patients with narcolepsy. METHODS: 38 drug-naive narcoleptic patients, 25 males and 13 females, aged 21 +/- 6.5, and 44 age-, sex ratio-, and BMI-matched normal persons underwent polysomnography (PSG) and multiple sleep latency test (MSLT) during one night sleep. Conventional visual scoring of the polysomnograms was performed according to the international. RESULTS: The sleep latency of the patients was 5.6 min, however, 30 patients (79%) complained of fragmented nocturnal sleep and difficulty to fall asleep again. The sleep efficiency of the narcoleptics was 81.7% +/- 12.5%, significantly lower than that of the normal persons (87.1% +/- 7.9%, P = 0.029). The non-rapid eye movement (NREM) I sleep accounted for (21.5 +/- 12.2)% in the patients, a proportion significantly higher than that of the normal persons [(10.3 +/- 6.3)%, P = 0.000]). The AHI of the patients was 0.6 +/- 1.3 times/h, not significantly different from that of the normal persons (0.5 +/- 1.1 times/h). Although the rapid eye movement (REM) period and eye movement density of the narcoleptics were significantly increased, their REM period duration was not significantly different from that of the normal subjects (17.7% +/- 6.9% vs 18.9% +/- 5.5%, P = 0.23), probably due to the interruption of REM sleep by more frequent arousals in narcoleptics. PSG did not show significant periodic leg movements in these 2 groups. CONCLUSION: One of the important symptoms of narcolepsy, night sleep disturbance may contribute to the pathological sleepiness of narcolepsy during daytime.