Publications by authors named "Suxia Wang"

104 Publications

The clinical and pathological relevance of waxy casts in urine sediment.

Ren Fail 2022 Dec;44(1):1038-1044

Renal Division, Peking University First Hospital, Institute of Nephrology, Peking University, Beijing, China.

Although casts in urine may imply the underlying pathogenesis and the diagnosis, the waxy cast is poorly understood yet. We aim to investigate the association between waxy casts and clinicopathological indices. Patients undergone renal biopsy and urine sediment examination were enrolled. Waxy casts referred to those presented with a homogeneous melted wax appearance and pre-waxy casts referred to those in which one or more segments demonstrated a waxy-cast appearance. Multivariable logistic regression was used to assess the factors associated with waxy casts. In 1282 patients, the detection rate of waxy casts was 26.3%. If either waxy or pre-waxy cast was considered as a diagnostic marker for renal insufficiency (eGFR < 60 ml/min/1.73 m), the sensitivity was 0.58 and the specificity was 0.88. If the only waxy cast was considered as the diagnostic marker, the sensitivity was 0.29 and the specificity was 0.97. The patients with waxy or pre-waxy casts had higher blood pressure, more proteinuria, and worse renal function. Waxy or pre-waxy cast was independently associated with eGFR (odds ratio: 0.73 per 10 mL/min/1.73 m increase, 95% confidence interval: 0.69-0.77,  < 0.001), proteinuria (odds ratio: 1.07 per 1 g/day increase, 95% confidence interval: 1.03-1.10,  < 0.001) and pathological lesions. Waxy or pre-waxy casts are closely related to impaired renal function. Their presence is a specific indicator of renal insufficiency but is not sensitive enough.
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http://dx.doi.org/10.1080/0886022X.2022.2088388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246008PMC
December 2022

Hypercalciuria may predict better response to immunosuppressive therapy in renal sarcoidosis: a case series.

J Nephrol 2022 Jun 13. Epub 2022 Jun 13.

Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, No.8 Xishiku Street, Xicheng District, Beijing, China.

Background: Renal sarcoidosis is a rare cause of tubulointerstitial nephritits (TIN). The clinical and pathological characteristics, as well as outcomes, of renal sarcoidosis remain unclear.

Methods: This single-center study retrospectively analyzed 18 patients affected by sarcoidosis with tubulointerstitial nephritis (TIN) and 53 patients with tubulointerstitial nephritis  not related to sarcoidosis. Patients were further stratified into the granulomatous (12 sarcoidosis and 6 non-sarcoidosis) and non-granulomatous (6 sarcoidosis and 47 non-sarcoidosis) TIN groups.

Results: Half of the patients with renal sarcoidosis had signs of acute kidney injury at kidney biopsy, 94% of whom presented with extra-renal involvement. The prevalence of hypercalcemia, hypercalciuria, and elevated serum angiotensin-converting enzyme levels was 27.6%, 33.3%, and 31.3%, respectively. Renal sarcoidosis patients with eGFR < 30 mL/min/1.73 m scored higher for total chronic tubulointerstitial injury (p = 0.044) and glomerular sclerosis (p = 0.027). Compared to non-sarcoidosis patients, higher urinary calcium levels (for patients with GFR [Formula: see text] 40 mL/min/1.73 m, p = 0.034), lower scores of acute tubular injury (p = 0.008), and more prominent glomerular sclerosis were observed in renal sarcoidosis. Similar characteristics of chronicity and hypercalciuria were also identified in granulomatous interstitial nephritis; however, interstitial inflammation was obvious (p = 0.001). Patients with renal sarcoidosis were initially treated with corticosteroids. Five patients receiving immunosuppressive agents showed better long-term renal recovery. High 24-h urine calcium (adjusted by weight) was identified as a factor associated with long-term remission.

Conclusion: Renal sarcoidosis is a systemic disease of insidious onset and chronic progression, sharing similar features of chronicity and hypercalciuria with granulomatous interstitial nephritis of other cause. Hypercalciuria may predict a better response to immunosuppressive therapy, presumably indicating active interstitial inflammation; thus, strengthened immunosuppression might be considered.
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http://dx.doi.org/10.1007/s40620-022-01360-7DOI Listing
June 2022

Crystal-induced collapsing podocytopathy and light chain proximal tubulopathy in monoclonal gammopathy of renal significance.

J Nephrol 2022 Jun 10. Epub 2022 Jun 10.

Ultrastructural Pathology and Bioimaging Laboratory, "Victor Babes" Institute of Pathology, Bucharest, Romania.

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http://dx.doi.org/10.1007/s40620-022-01362-5DOI Listing
June 2022

Clinicopathological characteristics of high-altitude polycythemia-related kidney disease in Tibetan inhabitants.

Kidney Int 2022 07 2;102(1):196-206. Epub 2022 May 2.

Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China; Renal Pathological Center, Institute of Nephrology, Peking University, Beijing, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China; Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China.

High-altitude polycythemia (HAPC) is a clinical syndrome that occurs in native inhabitants or long-term residents living at altitude. The kidney is one of the most affected organs. However, the clinical and kidney histopathological profiles of HAPC-related kidney disease have rarely been reported. Here, we report kidney biopsy-based clinicopathological study on this disease. HAPC was defined as excessive erythrocytosis [females, hemoglobin 190 g/L or more; males, 210 g/L or more] in patients living above an altitude of 2500 m for more than ten years. A total of 416 Tibetan patients underwent kidney biopsy between January 1, 2016, and November 31, 2020. Of these patients 17 met the diagnostic criteria for HAPC-related kidney disease. Clinically, these patients had a median urinary protein level of 2.5 g/24-hour (range 1.81-6.85). Twelve patients had hyperuricemia, nine had hypertension, and three had kidney insufficiency. On histopathology, glomerular hypertrophy, glomerular basement membrane thickening, podocyte foot process effacement, segmental glomerulosclerosis and global glomerulosclerosis were the main features. Extraglomerular arterial/arteriolar lesions were common, presenting as intimal fibrosis, hyalinosis and endothelial cell swelling/subintimal edema. Expansion of the arterial/arteriolar medial wall area characterized by smooth muscle cell proliferation was clearly observed, potentially indicating vascular remodeling. Hypoxia-inducible factor 2α was expressed in the kidney tissues of these patients. Thus, the pathological changes of HAPC-related kidney disease encompassed both glomerular and extraglomerular vascular lesions, suggesting a key role of both chronic hypoxia itself and secondary hemodynamic changes in the pathogenesis of this disease.
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http://dx.doi.org/10.1016/j.kint.2022.03.027DOI Listing
July 2022

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits: an entity associated with distinct diseases and comparison between IgG1 and IgG3 subtypes.

J Nephrol 2022 Apr 23. Epub 2022 Apr 23.

Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.

Objectives: The aim of the study was to investigate the clinicopathological characteristics and prognosis of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) and determine the differences between PGNMID associated with extrarenal disease and without clear etiology as well as the differences between IgG1 and IgG3 subtypes.

Methods: Data from 46 patients with PGNMID observed from January 2014 to September 2021 in Peking University First Hospital were retrospectively analyzed, including 36 patients without clear etiology (Group A) and 10 patients with extrarenal disease (Group B).

Results: At presentation patients showed proteinuria (95.7%), hematuria (89.1%), renal insufficiency (73.9%), and hypocomplementemia of C3 or C4 (35.6%). Monoclonal immunoglobulin or cell clones were detected in 22.2% of patients (10/45). The monoclonal immunoglobulins deposited in kidney were IgG3 in 40 patients, IgG1 in 5, and IgM in one. Monoclonal IgG1 deposits were more common in Group B than in Group A (4/10 vs. 1/36, p = 0.006). The intensity of glomerular C3 deposition and the frequency of subendothelial deposits in IgG3 subtype were significantly higher than those in IgG1 subtype. During a median follow-up time of 12.2 (range 1-61) months, a higher level of serum creatinine at biopsy and a higher percentage of global glomerulosclerosis were independent predictors of end-stage kidney disease.

Conclusions: PGNMID associated with extrarenal disease was more likely to have monoclonal IgG1 deposits. PGNMID of IgG3 subtype differs from IgG1 subtype by higher intensity of glomerular C3 deposition and higher frequency of subendothelial deposits. Serum creatinine and global glomerulosclerosis were independent prognostic predictors of ESKD in PGNMID.
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http://dx.doi.org/10.1007/s40620-022-01317-wDOI Listing
April 2022

Potential Involvement of Complement Activation in Kidney Vascular Lesions of Arterionephrosclerosis.

Front Med (Lausanne) 2022 31;9:836155. Epub 2022 Mar 31.

Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, National Health and Family Planning Commission of the People's Republic of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, China.

Background: Complement dysregulation has been implicated in the pathogenesis of malignant nephrosclerosis with typical pathological manifestation as thrombotic microangiopathy (TMA) in recent studies. The aim of the present study was to evaluate the potential role of complement activation in arterionephrosclerosis, the major pathological change in benign hypertensive nephrosclerosis.

Methods: Patients with biopsy-proven arterionephrosclerosis from 2010 to 2018 in our center were retrospectively enrolled in the present study. The clinical data were retrieved from the medical chart record. The pathological changes of renal biopsy were semiquantitatively evaluated. The ratio of inner-/outer-luminal diameter of the arterioles was calculated to evaluate the degree of arteriosclerosis. Immunohistochemical staining of CD34 and CD68 was adopted to evaluate peritubular capillary (PTC) density and macrophage infiltration, respectively. Complement components, including C3d, C4d, C1q, and C5b-9, were detected by immunohistochemical staining in paraffin-embedded sections. IgM and albumin were detected by immunofluorescence staining in frozen renal tissues.

Results: Fifty-two patients were enrolled. The mean age was 45.0 ± 12.7 years, with 39 (75%) males. The median duration of hypertension was 66 months (IQR: 24-138 months). A total of 950 arterioles were evaluated, with a mean ratio of the inner/outer luminal diameter of 0.43 ± 0.05. The ratio of the inner-/outer-luminal diameter correlated with eGFR ( = 0.341, = 0.013), sclerotic/ischemic glomerular lesions ( = -0.364, = 0.008) and PTC density ( = 0.426, = 0.002). Seventy-four percent (703/950) of the evaluated arterioles had C3d deposition with various patterns and intensities. The percentage of C3d-positive arterioles ranged from 63.6 to 100.0% in each specimen. The ratio of the inner/outer luminal diameter of arterioles correlated with the intensity of C3d deposition ( = -0.174, = 0.001). Infiltration of macrophages was observed around C3d-positive arterioles. The percentage of C3d-positive arterioles was correlated with macrophage infiltration in each specimen ( = 0.330, = 0.018). Occasional C4d-positive staining on arterioles was observed with no deposition of C1q or C5b-9 in arterionephrosclerosis specimens.

Conclusion: Our findings provide evidence for potential complement activation in the pathogenesis of vascular lesions in arterionephrosclerosis.
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http://dx.doi.org/10.3389/fmed.2022.836155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008485PMC
March 2022

Human Amnion Epithelial Cells and Their Derived Exosomes Alleviate Sepsis-Associated Acute Kidney Injury Mitigating Endothelial Dysfunction.

Front Med (Lausanne) 2022 24;9:829606. Epub 2022 Mar 24.

Renal Division, Peking University First Hospital, Beijing, China.

Background: Sepsis is characterized by organ dysfunction resulting from a patient's dysregulated response to infection. Sepsis-associated acute kidney injury (S-AKI) is the most frequent complication contributing to the morbidity and mortality of sepsis. The prevention and treatment of S-AKI remains a significant challenge worldwide. In the recent years, human amnion epithelial cells (hAECs) have drawn much attention in regenerative medicine, yet the therapeutic efficiency of hAECs in S-AKI has not been evaluated.

Methods: Septic mice were induced by cecal ligation and puncture (CLP) operation. hAECs and their derived exosomes (EXOs) were injected into the mice tail vein right after CLP surgery. The 7-day survival rate was observed. Serum creatinine level was measured and H&E staining of tissue sections were performed 16 h after CLP. Transmission electron microscopy was used to examine the renal endothelial integrity in CLP mice. Human umbilical vein endothelial cells (HUVECs) were treated with lipopolysaccharide (LPS) and EXOs. Zonula occludens-1 (ZO-1) localization was observed by immunofluorescence staining. Expression of phosphor-p65 (p-p65), p65, vascular cell adhesion molecule-1 (VCAM-1), and ZO-1 in the kidney were determined by Western blot.

Results: hAECs decreased the mortality of CLP mice, ameliorated septic injury in the kidney, and improved kidney function. More precisely, hAECs suppressed systemic inflammation and maintained the renal endothelial integrity in septic animals. EXOs from hAECs exhibited similar renal protective effects as their parental cells. EXOs maintained endothelial cell adhesion junction and inhibited endothelial cell hyperactivation . Mechanistically, EXOs suppressed proinflammatory nuclear factor kappa B (NF-κB) pathway activation in LPS-treated HUVECs and in CLP mice kidneys.

Conclusion: Our results indicate that hAECs and their derived EXOs may ameliorate S-AKI the prevention of endothelial dysfunction in the early stage of sepsis in mice. Stem cell or exosome-based therapy targeting endothelial disorders may be a promising alternative for treatment of S-AKI.
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http://dx.doi.org/10.3389/fmed.2022.829606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989462PMC
March 2022

[A child with diffuse mesangial sclerosis caused by a missense mutation of TRPC6 gene].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2022 Mar;39(3):325-329

Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.

Objective: To explore the genetic etiology and clinical outcome of a child with steroid-resistant nephrotic syndrome and diffuse mesangial sclerosis.

Methods: Genomic DNA was extracted from peripheral blood leukocytes of the proband and his parents. Targeted capture - next generation sequencing and Sanger sequencing were carried out. Candidate variant was verified by segregation analysis in his family.

Results: A heterozygous missense variant of the TRPC6 gene, namely c.325G>A (p.Gly109Ser), was detected in the proband. The same variant was not detected in either parent. According to the guidelines for the interpretation of sequence variants developed by American College of Medical Genetics and Genomics, the variant was predicted as pathogenic.

Conclusion: The missense variant of the TRPC6 gene probably underlay the diffuse mesangial sclerosis in this patient. Above finding has expanded the phenotypic spectrum of the TRPC6 gene.
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http://dx.doi.org/10.3760/cma.j.cn511374-20201211-00868DOI Listing
March 2022

Case Report: Chronic Lymphocytic Leukemia With Recurrent Complement-Mediated Thrombotic Microangiopathy and C3 Glomerulonephritis.

Front Med (Lausanne) 2022 10;9:813439. Epub 2022 Feb 10.

Laboratory of Electron Microscopy, Ultrastructural Pathology Center, Peking University First Hospital, Beijing, China.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a monoclonal B cell lymphocytosis that produces nephrotoxic monoclonal immunoglobulin (MIg). However, the role of MIg in CLL and how it affects CLL patient survival are still unknown. Here, we report a case of MIg with renal significance (MGRS) associated with CLL. A 59-year-old Chinese woman complaining of abdominal pain, skin purpura, and typical soy-colored urine was admitted to the hospital for investigation. Laboratory tests revealed that she had microangiopathic hemolytic anemia, thrombocytopenia, acute kidney injury (AKI), and hypocomplementemia. She also reported cryoglobulinemia, thrombotic microangiopathy (TMA), and AKI 2 years previously. Peripheral blood smears at that time showed 4% schistocytes, a negative Coombs' test, and elevated lactate dehydrogenase (LDH). Based on a diagnosis of complement-mediated TMA, the patient was treated by plasmapheresis and achieved clinical disease remission. However, the serum hypocomplement 4 and cryoglobulinemia persisted. Further investigation showed elevated B lymphocytes and monoclonal serum IgMκ; however, the cryoprecipitate contained monoclonal IgMκ and polyclonal IgG, as well as immunoglobulins κ and λ. After plasmapheresis, her LDH, platelets, and complement 3 (C3) levels returned to normal. Biopsies of the bone marrow and an enlarged subclavicular lymph node revealed CLL/SLL. Renal pathological findings indicated significant arteriolar endothelial cells myxoid edema and glomerular endothelial cells swelling, however no thromboli, cryoglobulin formation and vasculitis were observed. We also found mild mesangial proliferative C3 glomerulonephritis and renal interstitial CLL cells infiltration. Collectively, these clinical and pathological manifestations were attributed to monoclonal IgMκ, which triggered C3 activation. MGRS associated with CLL was finally confirmed. Six cycles of rituximab, cyclophosphamide, verodoxin, and dexamethasone therapy were administered, after which she received ibrutinib. The patient experienced disease remission, and her serum C4 level returned to normal. Cryoglobulin and IgMκ were not detected. This is a special presentation of CLL/SLL with monoclonal IgMκ, which is a type of MGRS. Activation of the complement system by MIg led to TMA with C3 glomerulonephritis. Treatment for TMA and CLL/SLL should be initiated in a timely manner to improve patient prognosis.
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http://dx.doi.org/10.3389/fmed.2022.813439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866726PMC
February 2022

Human Amniotic Epithelial Cells and Their Derived Exosomes Protect Against Cisplatin-Induced Acute Kidney Injury Without Compromising Its Antitumor Activity in Mice.

Front Cell Dev Biol 2021 3;9:752053. Epub 2022 Feb 3.

Renal Division, Renal Pathology Center, Peking University First Hospital, Beijing, China.

Cisplatin is a widely used chemotherapeutic drug, whereas the clinical application is greatly limited by its nephrotoxic side effect. Currently, there has been no effective treatment to prevent cisplatin-induced acute kidney injury (cisplatin-AKI). Human amniotic epithelial cells (hAECs) and their derived exosomes (EXOs) have been proven to effectively protect against ischemia reperfusion-induced AKI, yet their roles in cisplatin-AKI are still unknown. C57BL/6J mice were given two doses of cisplatin at 20 or 15 mg/kg of body weight to induce AKI with or without mortality. hAECs or EXOs were injected via tail vein 1 day after cisplatin administration. Serum and kidney tissues were collected on the fourth day after 15 mg/kg cisplatin treatment to explore the nephro-protective effects of hAECs and EXOs on cisplatin-AKI. Lung cancer xenograft model was built by subcutaneous injection of A549 cells into BALB/c nude mice to evaluate the effect of hAECs or EXOs on cisplatin chemotherapy. Cisplatin nephrotoxicity was significantly attenuated by hAECs and EXOs as evidenced by reduced mortality rate and decreased serum creatinine (sCr) and reduced tubular injury score. hAECs or EXOs exerted the nephro-protective effects via suppression of TNF-α/MAPK and caspase signaling pathways. In the A549 lung cancer xenograft mouse model, administration of hAECs or EXOs did not promote tumor growth or compromise the therapeutic effects of cisplatin on tumors. This study is the first to demonstrate that hAECs and their derived exosomes have nephro-protective effects in cisplatin-AKI . Importantly, neither hAECs nor EXOs compromise the antitumor activity of cisplatin. These results potentially support the use of hAECs and their derived EXOs as nephro-protectors against cisplatin-induced nephrotoxicity clinically.
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http://dx.doi.org/10.3389/fcell.2021.752053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851426PMC
February 2022

Single Cell RNA Sequencing Identifies a Unique Inflammatory Macrophage Subset as a Druggable Target for Alleviating Acute Kidney Injury.

Adv Sci (Weinh) 2022 04 3;9(12):e2103675. Epub 2022 Feb 3.

Renal Division, Peking University Institute of Nephrology, Key Laboratory of Renal Disease-Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment (Peking University)-Ministry of Education of China, Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases-Chinese Academy of Medical Sciences, Peking University First Hospital, Xishiku Street #8, Beijing, 100034, China.

Acute kidney injury (AKI) is a complex clinical disorder associated with poor outcomes. Targeted regulation of the degree of inflammation has been a potential strategy for AKI management. Macrophages are the main effector cells of kidney inflammation. However, macrophage heterogeneity in ischemia reperfusion injury induced AKI (IRI-AKI) remains unclear. Using single-cell RNA sequencing of the mononuclear phagocytic system in the murine IRI model, the authors demonstrate the complementary roles of kidney resident macrophages (KRMs) and monocyte-derived infiltrated macrophages (IMs) in modulating tissue inflammation and promoting tissue repair. A unique population of S100a9 Ly6c IMs is identified as an early responder to AKI, mediating the initiation and amplification of kidney inflammation. Kidney infiltration of S100A8/A9 macrophages and the relevance of renal S100A8/A9 to tissue injury is confirmed in human AKI. Targeting the S100a8/a9 signaling with small-molecule inhibitors exhibits renal protective effects represented by improved renal function and reduced mortality in bilateral IRI model, and decreased inflammatory response, ameliorated kidney injury, and improved long-term outcome with decreased renal fibrosis in the unilateral IRI model. The findings support S100A8/A9 blockade as a feasible and clinically relevant therapy potentially waiting for translation in human AKI.
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http://dx.doi.org/10.1002/advs.202103675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036000PMC
April 2022

Clinicopathological and molecular study of 10 salivary gland clear cell carcinomas, with emphasis on rare cases with high grade transformation and occurring in uncommon sites.

Diagn Pathol 2022 Jan 30;17(1):18. Epub 2022 Jan 30.

Department of Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Head and Neck Molecular Diagnostic Pathology, Beijing, 100730, China.

Background: As a rare salivary gland malignancy, clear cell carcinoma (CCC) is easily misdiagnosed. This study identified the features that allow better recognition of the clinicopathological and molecular characteristics and the prognosis of CCC, focusing on high-grade transformation (HGT) in this tumor and cases arising in uncommon sites.

Methods: Clinicopathological and follow-up data for 10 CCC samples were retrieved. Immunohistochemical (IHC) staining was performed, and fluorescence in situ hybridization (FISH) was used to detect EWSR1 gene rearrangements, EWSR1-ATF1 gene fusions, and MAML2 gene rearrangements.

Results: Histologically, typical CCCs comprised bland polygonal or round cells with clear cytoplasm. In contrast with typical CCCs, HGT tumor cells exhibited nuclear pleomorphism, high nuclear-to-cytoplasmic ratios, high mitotic activity, and necrosis. Rare morphologic features such as pseudopapillae, gland-like spaces, and entrapped ducts were also observed. Occasionally, tumors involving the oral cavity might arise from the overlying epithelium of the mucosal surface. Immunohistochemically, all the cases expressed p63, p40, and CK5/6, while myoepithelial-related markers were uniformly negative in all cases. HGT exhibited a wild type p53 expression pattern. FISH demonstrated EWSR1 rearrangement (10/10) and EWSR1-ATF1 fusion (4/5); however, MAML2 remained intact (0/3).

Conclusions: CCCs with HGT or occurring in uncommon sites are extremely rare. Combining morphology based IHC and molecular detection provided reliable evidence that the HGT component represented a transformation of CCC rather than the coexistence of another tumor and helped differentiating CCCs in uncommon sites from their mimics, avoiding potential misdiagnosis and inappropriate therapy. The overall prognosis for CCCs is good, except for the HGT cases, which needed continued treatment.
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http://dx.doi.org/10.1186/s13000-022-01200-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8802448PMC
January 2022

Rapidly progressive iga nephropathy: clinicopathological characteristics and outcomes assessed according to the revised definition of the KDIGO 2021 guideline.

Nephrol Dial Transplant 2022 Jan 10. Epub 2022 Jan 10.

Renal Division, Department of Medicine, Peking University First Hospital; Peking University Institute of Nephrology; Key Laboratory of kidney Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education.

Background: Rapidly progressive IgA nephropathy (RPIgAN) is a severe clinical phenotype of IgAN, associated with a poor outcome. The recently published KDIGO 2021 Guideline for the Management of Glomerular Diseases has proposed a new definition for RPIgAN, which is based simply on a ≥ 50% decline in eGFR ≤ 3 months.

Methods: In 1,677 IgAN patients followed at a single centre in China, we evaluated the utility of this new definition to identify the highest risk IgAN patients who might be suitable for combination immunosuppressive therapy.

Results: The proportion of a ≥ 50% decline in eGFR ≤ 3 months was 5.2%. The majority of these patients had reversible causes, only 2.3% (39/1,677) meeting the KDIGO 2021 criteria for RPIgAN. These patients had a significantly higher risk for ESKD than non-RPIgAN patients (log rank P < 0.001). RPIgAN was an independent risk factor for ESKD (hazard ratio [HR] 3.99; 95% confidence interval [CI] 2.25 - 7.09; P < 0.001). A minority of the RPIgAN patients (25.6%) had ≥ 50% crescents. There was no significant difference in the risk for ESKD between patients in the RPIgAN group with ≥ 50% crescents and ˂ 50% crescents (log rank P = 0.27). Patients with RPIgAN and ≥ 50% crescents had a higher risk for ESKD than patients with non-RPIgAN and ≥ 50% crescents (log rank P = 0.04).

Conclusions: These data support the validity of the KDIGO 2021 definition but require independent validation in other non-Chinese cohorts.
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http://dx.doi.org/10.1093/ndt/gfac004DOI Listing
January 2022

57-year-old woman with purpura fulminans and acute kidney injury.

J Clin Pathol 2021 Dec 10. Epub 2021 Dec 10.

Renal Pathological Center, Institute of Nephrology, Peking University, Beijing, China

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http://dx.doi.org/10.1136/jclinpath-2020-207020DOI Listing
December 2021

ELK1-induced up-regulation of KIF26B promotes cell cycle progression in breast cancer.

Med Oncol 2021 Nov 24;39(1):15. Epub 2021 Nov 24.

Key Laboratory for Experimental Teratology of Ministry of Education, Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan Wen Hua Xi Road 44, Jinan, 250012, Shandong, China.

KIF26B is a member of the kinesin superfamily that is up-regulated in various tumors, including breast cancer (BC), which can promote tumor progression. This study aimed to investigate the potential function of KIF26B in BC, and the underlying mechanisms, focusing mainly on cell proliferation. KIF26B expression was examined in BC tissue samples obtained from 99 patients. Then, we performed MTS, EdU and flow cytometry assays to detect cell proliferation, and western blotting to measure the expression of cell cycle-related proteins in MDA-MB-231 and MDA-MB-468 cells following KIF26B knockdown. Promoter analysis was used to study the upstream regulatory mechanism of KIF26B. KIF26B was upregulated in BC tissues. High expression of KIF26B was associated with clinicopathological parameters, such as positive lymph node metastasis, higher tumor grade, and higher proliferative index in BC. Furthermore, knockdown of KIF26B expression inhibited MDA-MB-231 and MDA-MB-468 cell proliferation, arresting cells in the G phase of the cell cycle in vitro. Similarly, KIF26B silencing decreased the expression levels of Wnt, β-catenin, and cell cycle-related proteins such as c-Myc, cyclin D1, and cyclin-dependent kinase 4, while increasing the expression of p27. Moreover, ELK1 could bind to the core promoter region of KIF26B and activate its transcription. KIF26B acts as an oncogene in BC by regulating multiple proteins involved in the cell cycle. ELK1 activates KIF26B transcription.
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http://dx.doi.org/10.1007/s12032-021-01607-6DOI Listing
November 2021

Clinicopathological Patterns and Predictors of the Functional Restoration of Immunoglobulin G4-Related Kidney Disease: A Chinese Single-Center Cohort Study.

Front Med (Lausanne) 2021 6;8:736098. Epub 2021 Oct 6.

Department of Nephrology, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic immunoreactivity-based fibro-inflammatory disease. Immunoglobulin G4-related kidney disease (IgG4-RKD) is a frequently overlooked diagnosis. This study aimed to describe IgG4-RKD and examine the factors relevant to the renal outcomes of IgG4-RD. We studied a prospective IgG4-RKD cohort between January 2012 and December 2020 with close follow-up. Clinicopathologic data at kidney biopsy were collected and analyzed. We aimed to explore independent risk factors for long-term renal outcome and disease relapse. Patients with an eGFR<45 ml/min per 1.73m at 12 months were defined as having poor outcomes. The included 42 patients with IgG4-RKD had a mean age of 58.5 ± 8.7 years (male-to-female ratio = 5:1). The IgG4-RD responder index (RI) was 12.2 ± 3.3. A total of 66.7% of the patients presented with acute on kidney disease or acute on chronic kidney disease. Eight patients (19.0%) showed nephrotic-range proteinuria, and nine (21.4%) had high-titer IgG4-autoantibodies, including antineutrophil cytoplasmic antibody and anti-phospholipase A2 receptor. A kidney biopsy was conducted in 40 patients. Thirty-seven (90.0%) patients were diagnosed with IgG4-related tubulointerstitial nephritis, and 19 (47.5%) of them had concurrent glomerular diseases (membranous nephropathy [MN], = 3; crescentic glomerulonephritis [CrGN], = 11; diabetic kidney disease, = 3; and both MN and CrGN, = 2). IgG4-RD RI had a close relationship with serum C3 ( = -0.509, = 0.001), C4 ( = -0.314, = 0.049) levels, and peripheral blood eosinophil count (PBEC; = 0.377, = 0.024), factors that were not included in RI scores. Correlation analysis disclosed that IgG4-RD RI ( = 0.422, = 0.007), organs involved ( = 0.452, = 0.003), and C3 ( = -0.487, = 0.002) were correlated with the percentage decrease of serum creatinine at 1 month. However, multivariate regression analysis failed to identify any clinicopathological parameters that could predict short-term renal restoration and IgG4-RKD relapse. Ten out of 29 variables, of most importance, were identified by the least absolute shrinkage and selection operator (LASSO) regression analysis. By multivariate logistic regression a higher serum IgG4 (OR = 0.671, = 0.010), IgG1 (OR = 1.396, = 0.049), IgG3 (OR = 19.154, = 0.039), and erythrocyte sedimentation rate (ESR; OR = 1.042, = 0.032) were found to be independent factors for poor long-term outcome. Conventional immunosuppressive medications and/or rituximab were prescribed, and in 83.3% of the patients, the kidney function improved. Repeat kidney biopsies confirmed the remission of interstitial inflammation in two patients under immunosuppressive therapy. However, the disease relapse rate was as high as 31.0%. We strongly recommend a kidney biopsy in active IgG4-RD, especially when there is proteinuria and renal dysfunction, because concurrent glomerular involvement and active interstitial inflammation should be assessed. A higher serum IgG1, IgG3, and ESR were independent factors for the poor long-term renal outcome; however, elevated IgG4 predicted a good renal prognosis, and appropriate and timely immunosuppressive therapy can help achieve a better prognosis.
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http://dx.doi.org/10.3389/fmed.2021.736098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526789PMC
October 2021

The effect of immunosuppressive therapy in patients with fibrinoid necrosis lesions in a large cohort of patients with IgA nephropathy.

J Nephrol 2022 05 21;35(4):1079-1089. Epub 2021 Oct 21.

Renal Division, Department of Medicine, Key Laboratory of Renal Disease, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Ministry of Health of China, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, 100034, People's Republic of China.

Background: Fibrinoid necrosis is considered one of the active pathological lesions in IgA nephropathy. Whether patients with IgA nephropathy with fibrinoid necrosis lesions benefit from immunosuppressive therapy in terms of long-term outcomes remains uncertain. This study aimed to evaluate the response to immunosuppressive therapy in patients with fibrinoid necrosis lesions in a large cohort of patients with IgA nephropathy.

Methods: A total of 1325 patients with kidney biopsy-proven IgA nephropathy from 1994 to 2016 were recruited from the Peking University First Hospital IgA Nephropathy Database. The clinicopathological characteristics of patients with fibrinoid necrosis lesions and the effect of immunosuppressive therapy on patients with fibrinoid necrosis lesions alone or in those with fibrinoid necrosis together with crescents or endocapillary hypercellularity lesions were analyzed.

Results: In total, 107/1325 (8.1%) patients showed fibrinoid necrosis lesions, and 92/107 (86.0%) of these patients showed fibrinoid necrosis associated either with cellular/fibrocellular crescents or endocapillary hypercellularity lesions. The presence of fibrinoid necrosis together with crescents or endocapillary hypercellularity was an independent risk factor for the kidney composite endpoint (HR, 2.11; 95% CI, 1.16-3.84; P = 0.02) in patients without immunosuppression, while for those receiving immunosuppressive therapy, kidney outcome was improved (HR, 0.80; 95% CI, 0.46-1.39; P = 0.42). However, the predictive value of fibrinoid necrosis lesions alone did not change significantly between patients with and without immunosuppressive therapy.

Conclusions: The presence of fibrinoid necrosis with crescents or endocapillary hypercellularity lesions together, but not fibrinoid necrosis lesions alone, was a pathological indicator of patients who may benefit from immunosuppressive therapy.
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http://dx.doi.org/10.1007/s40620-021-01176-xDOI Listing
May 2022

The pathological features of leukemic cells infiltrating the renal interstitium in chronic lymphocytic leukemia/small lymphocytic lymphoma from a large single Chinese center.

Diagn Pathol 2021 Jul 4;16(1):59. Epub 2021 Jul 4.

Renal Pathology Center, Institute of Nephrology, Peking University, Beijing, 100034, People's Republic of China.

Background: Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is rare in Asians, and patients with CLL/SLL seldomly undergo kidney biopsy. The histopathological features and clinical relevance of tubulointerstitial injury in CLL/SLL have not been extensively characterized. Hence, we attempted to describe the clinical characteristics, renal pathology and clinical outcome of a well-characterized population of CLL/SLL patients with CLL cell infiltration in the renal interstitium from a large single center in China.

Methods: Between January 1st, 2010 and September 31st, 2020, 31946renal biopsies were performed at Peking University First Hospital, and 10 CLL/SLL patients with CLL cell infiltration in the renal interstitium were included. Complete clinical data were collected from these 10 patients, and renal specimens were examined by routine light microscopy, immunofluorescence and electron microscopy.

Results: The extent of the infiltrating CLL cells in patients with CLL/SLL varied among different patients and ranged from 10 to 90% of kidney parenchyma. Six (60%) of 10 patients presented with an extent of infiltrating CLL cells ≥50%. Interestingly, we found that three patients (3/10, 30%) expressed monoclonal immunoglobulins in the infiltrating CLL cells, and special cytoplasmic crystalline structures were found in two of the three patients by electron microscopy for the first time. Severe renal insufficiency (Scr ≥200 μmol/L) was associated with ≥50% interstitial infiltration of CLL cells in the renal interstitium.

Conclusions: The current study confirmed that CLL cells infiltrating the renal interstitium can directly secrete monoclonal immunoglobulins, indicating that the interstitial infiltrating CLL cells possibly cause renal injury directly by secreting monoclonal immunoglobulins in situ. This finding may prove a new clue to elucidate the pathogenetic mechanism of renal injury involved with CLL/SLL.
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http://dx.doi.org/10.1186/s13000-021-01120-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254985PMC
July 2021

[Determination of tranexamic acid in essential cosmetics by pre-column derivatization capillary electrophoresis coupled with electrogenerated chemiluminescence detection].

Se Pu 2020 Aug;38(8):968-974

College of Chemistry and Chemical Engineering, Northwest Normal University, Key Laboratory of Bioelectrochemistry and Environmental Analysis of Gansu Province, Lanzhou 730070, China.

-Methylation of tranexamic acid yields an unique derivative, which generates strong co-luminescence signals in the presence of an electrochemiluminescence reagent such as Ru(bpy). Using this principle, we established a highly selective analytical method based on pre-column derivatization capillary electrophoresis coupled with electrogenerated chemiluminescence detection for determining the tranexamic acid content in essential cosmetics. The addition of a ternary ionic association gel, Mg-trehalose-SiO, in the components of background electrolyte greatly improved the electrophoretic separation efficiency. Under the optimized assay conditions, two electrophoretic peaks attributed to the derivatives of tranexamic acid and its internal standard (sarcosine) were completely separated in 500 s, and their electrophoretic peak intensities ratio showed a good linear relationship with the initial concentration of tranexamic acid in the range of 10-750 μmol/L (correlation coefficient =0.9993). The limit of detection was estimated to be 3.6 μmol/L (=3). Moreover, the internal standard method was further applied to the quantitative determination of tranexamic acid content in three kinds of toothpaste and two kinds of nutrient solutions in facial masks. The results showed that the average tranexamic acid content in three toothpaste samples was 4.05, 0.24, and 6.06 mg/g, while that in two facial masks was 51.3 and 7.98 mg/mL. The recoveries for the above-mentioned samples were within the range 92.5% to 104.0%, implying satisfactory results.
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http://dx.doi.org/10.3724/SP.J.1123.2019.12002DOI Listing
August 2020

Clinicopathological features and outcomes of coexistent light chain cast nephropathy and light chain deposition disease in patients with newly diagnosed multiple myeloma.

J Clin Pathol 2021 Jun 29. Epub 2021 Jun 29.

Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.

Aims: A varying proportion of patients with multiple myeloma suffer from more than one type of kidney disease simultaneously, of which the most common pattern is coexistent light chain cast nephropathy and light chain deposition disease (LCCN+LCDD). We investigated clinicopathological characteristics and outcomes of LCCN+LCDD in comparison with pure LCCN and pure LCDD.

Methods: We retrospectively analysed 45 newly diagnosed multiple myeloma patients with pure LCCN (n=26), LCCN +LCDD (n=9) and pure LCDD (n=10) between 2000 and 2019 at Peking University First Hospital.

Results: Pathologically, patients with LCCN+LCDD were more likely to have λ light chain isotype and presented atypical features of LCDD including less nodular glomerulosclerosis and less deposit distribution than patients with pure LCDD. In clinical characteristics, patients with LCCN +LCDD and patients with pure LCCN shared similar features. The death-censored renal survival in patients with LCCN +LCDD was similar to patients with pure LCCN but worse than patients with pure LCDD, but the overall survival was much better than patients with LCCN alone and similar to patients with pure LCDD. For patients with pure LCCN, the independent predictor of death-censored renal survival was lactate dehydrogenase, and the independent predictors of overall survival were the mean number of casts and serum albumin.

Conclusions: Patients with LCCN+LCDD had similar renal outcome compared with patients with pure LCCN but the overall survival is much better. Thus, for patients with LCCN, especially those with λ restriction, pathologists should carefully evaluate the kidney specimens to exclude the possibility of combined LCDD.
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http://dx.doi.org/10.1136/jclinpath-2021-207449DOI Listing
June 2021

Noninvasive Evaluation of Renal Hypoxia by Multiparametric Functional MRI in Early Diabetic Kidney Disease.

J Magn Reson Imaging 2022 02 28;55(2):518-527. Epub 2021 Jun 28.

Department of Radiology, Peking University First Hospital, Beijing, China.

Background: Renal hypoxia, which caused by a mismatch between oxygen delivery and oxygen demand, may be the primary pathophysiological pathway driving diabetic kidney disease (DKD). Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) could detect hypoxia, but can be limited in distinguishing increased oxygen consumption or decreased blood supply.

Purpose: To explore multiparametric functional MRI in evaluating mechanism of the hypoxia changes in early stage of DKD.

Study Type: Prospective.

Animal Model: Thirty-five New Zealand White rabbits were divided into control group (n = 5) and alloxan-induced diabetes mellitus (DM) groups (DM3 group: n = 15, DM7 group: n = 15).

Field Strength/sequence: 3 T MRI/BOLD, arterial spin labeling (ASL), and asymmetric spin-echo (ASE).

Assessment: The renal oxygenation level (R2*), renal blood flow (RBF), and oxygen extraction fraction (OEF) were evaluated by BOLD, ASL, and ASE MRI, respectively. The regions of interest were manually drawn including cortex, outer stripes of outer medulla (OS), and inner stripes of outer medulla (IS).

Statistical Tests: Analysis of variance, independent-sample t-test, and paired-sample t-test were applied for comparisons among groups, between groups, and within the same group. P < 0.05 was considered statistically significant.

Results: All renal regions of DM3 group at Day 3 after DM induction showed significantly higher R2* and OEF values compared to baseline. The RBF values showed no statistically significant difference (P = 0.62, 0.76, 0.09 in cortex, OS, and IS, respectively). For DM7 group at Day 7, R2*, OEF, and RBF values showed no statistically significant difference compared to baseline (P = 0.06, 0.05, 0.06 of R2*; 0.70, 0.64, 0.68 of OEF; and 0.33, 0.58, 0.48 of RBF in cortex, OS, and IS, respectively).

Data Conclusion: BOLD MRI could detect renal hypoxia in early stage of DKD rabbit model, which was mainly revealed by increased oxygen consumption, but not affected by renal blood flow change.

Level Of Evidence: 2 Technical Efficacy Stage: 1.
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http://dx.doi.org/10.1002/jmri.27814DOI Listing
February 2022

Nicotinamide Mononucleotide Attenuates Renal Interstitial Fibrosis After AKI by Suppressing Tubular DNA Damage and Senescence.

Front Physiol 2021 23;12:649547. Epub 2021 Mar 23.

Key Laboratory of Renal Disease, Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Ministry of Health of China, Beijing, China.

Acute kidney injury (AKI) is a worldwide health problem currently lacking therapeutics that directly promote renal repair or prevent the occurrence of chronic fibrosis. DNA damage is a feature of many forms of kidney injury, and targeting DNA damage and repair might be effective strategies for kidney protection in AKI. Boosting nicotinamide adenine dinucleotide (NAD) levels is thought to have beneficial effects on DNA damage repair and fibrosis in other organs. However, no kidney-related studies of such effects have been performed to date. Here, we have shown that NMN (an NAD precursor) administration could significantly reduce tubular cell DNA damage and subsequent cellular senescence induced by hydrogen peroxide and hypoxia in human proximal tubular cells (HK-2 cells). The DNA damage inhibition, antiaging and anti-inflammatory effects of NMN were further confirmed in a unilateral ischemia-reperfusion injury (uIRI) mouse model. Most importantly, the antifibrosis activity of NMN was also shown in ischemic AKI mouse models, regardless of whether NMN was administered in advance or during the recovery phase. Collectively, these results suggest that NMN could significantly inhibit tubular cell DNA damage, senescence and inflammation. NMN administration might be an effective strategy for preventing or treating kidney fibrosis after AKI.
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http://dx.doi.org/10.3389/fphys.2021.649547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021789PMC
March 2021

Osteocalcin and Abdominal Aortic Calcification in Hemodialysis Patients: An Observational Cross-Sectional Study.

Front Endocrinol (Lausanne) 2021 19;12:620350. Epub 2021 Mar 19.

Department of Medical Imaging, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, China.

Objectives: To investigate the serum level of osteocalcin (OC), also known as bone Gla protein, in maintenance hemodialysis (MHD) patients and its correlation with abdominal aortic calcification (AAC).

Methods: From July 2017 to February 2020, we enrolled 108 adult MHD patients. Routine fasting blood laboratory tests were performed before the start of the second hemodialysis in a week. Abdominal aortic calcification score (AACs) was assessed within 1 month. Pearson correlation and Logistic regression were used to analyze the data.

Results: The OC level was 231.56 (25.92,361.33) ng/ml, elevating significantly in this group of MHD patients. It had a positive correlation with serum phosphorus (r = 0.511, P = 0.001), intact parathyroid hormone(iPTH) (r = 0.594, P = 0.0001), fibroblast growth factor 23(FGF23) (r = 0.485, P = 0.003) and a negative correlation with age(r = -0.356, P = 0.039). Based on the AACs, patients were divided into two groups. Serum OC level were higher in patients with AACs≥5 (p=0.032). A multiple logistics regression analysis revealed that age (odds ratio [OR]1.14, P=0.005) and OC(OR=1.10, P=0.008)were risk factors for high AACs(≥5).

Conclusion: The study implicated that OC elevated significantly in this group of MHD patients.OC is positively correlated with phosphorus, iPTH, FGF23, and a negative correlation with age. OC was a risk factor for vascular calcification in this study, but this study did not classify osteocalcin as c-OC and unOC. Whether unOC is associated more directly with vascular calcification requires further study.
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http://dx.doi.org/10.3389/fendo.2021.620350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018234PMC
December 2021

Vps34 Inhibits Hepatocellular Carcinoma Invasion by Regulating Endosome-Lysosome Trafficking via Rab7-RILP and Rab11.

Cancer Res Treat 2022 Jan 26;54(1):182-198. Epub 2021 Mar 26.

Department of Pathology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.

Purpose: The role of vacuolar protein sorting 34 (Vps34), an indispensable protein required for cell vesicular trafficking, in the biological behavior of hepatocellular carcinoma (HCC) has yet to be studied.

Materials And Methods: In the present study, the expression of Vps34 in HCC and the effect of Vps34 on HCC cell invasion was detected both in vivo and in vitro. Furthermore, by modulating the RILP and Rab11, which regulate juxtanuclear lysosome aggregation and recycling endosome respectively, the underlying mechanism was investigated.

Results: Vps34 was significantly decreased in HCC and negatively correlated with the HCC invasiveness both in vivo and in vitro. Moreover, Vps34 could promote lysosomal juxtanuclear accumulation, reduce the invasive ability of HCC cells via the Rab7-RILP pathway. In addition, the deficiency of Vps34 in HCC cells affected the endosome-lysosome system, resulting in enhanced Rab11 mediated endocytic recycling of cell surface receptor and increased invasion of HCC cells.

Conclusion: Our study reveals that Vps34 acts as an invasion suppressor in HCC cells, and more importantly, the endosome-lysosome trafficking regulated by Vps34 has the potential to become a target pathway in HCC treatment.
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http://dx.doi.org/10.4143/crt.2020.578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8756109PMC
January 2022

Genotype-phenotype correlations and nephroprotective effects of RAAS inhibition in patients with autosomal recessive Alport syndrome.

Pediatr Nephrol 2021 09 27;36(9):2719-2730. Epub 2021 Mar 27.

Department of Pediatrics, Peking University First Hospital, No. 1 Xi An Men Da Jie, Beijing, 100034, China.

Background: Autosomal recessive Alport syndrome (ARAS) is caused by pathogenic variants in both alleles of either COL4A3 or COL4A4 genes. Reports on ARAS are rare due to small patient numbers and there are no reports on renin-angiotensin-aldosterone system (RAAS) inhibition therapy in ARAS.

Methods: Retrospective study in 101 patients with ARAS from Chinese Registry Database of Hereditary Kidney Diseases and European Alport Registry. Genotype-phenotype correlations and nephroprotective effects of RAAS inhibition in ARAS were evaluated.

Results: Median age was 15 years (range 1.5-46 years). Twelve patients progressed to stage 5 chronic kidney disease (CKD5) at median age 20.5 years. Patients without missense variants had both higher prevalence and earlier onset age of hearing loss, nephrotic-range proteinuria, more rapid decline of eGFR, and earlier onset age of CKD5 compared to patients with 1 or 2 missense variants. Most patients (79/101, 78%) currently are treated with RAAS inhibitors; median age at therapy initiation was 10 years and mean duration 6.5 ± 6.0 years. Median age at CKD5 for untreated patients was 24 years. RAAS inhibition therapy delayed CKD5 onset in those with impaired kidney function (T-III) to median age 35 years, but is undefined in treated patients with proteinuria (T-II) due to low number of events. No treated patients with microalbuminuria (T-I) progressed to CKD5. ARAS patients with 1 or 2 missense variants showed better response to treatment than patients with non-missense-variants.

Conclusions: Our study provides the first evidence for early use of RAAS inhibition therapy in patients with ARAS. Furthermore, genotype in ARAS correlates with response to therapy in favor of missense variants.
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http://dx.doi.org/10.1007/s00467-021-05040-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370956PMC
September 2021

Critically ill, tubular injury, delayed early recovery: characteristics of acute kidney disease with renal oxalosis.

Ren Fail 2021 Dec;43(1):425-432

Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China.

Objects: This study aimed to analyze the clinicopathological features of acute kidney disease (AKD) with renal oxalosis.

Methods: Data for biopsy-proven AKD with oxalosis diagnosed from Jan 2011 to Oct 2018 was collected. The underlying diseases, dietary habits, clinical and pathological characteristics of newly emerging kidney disease were analyzed. The long-term renal prognosis was observed.

Results: A total of 23 patients were included, comprised of 18 men and 5 women with a mean age of 51.6 ± 15.9 years. The peak Scr was 669.9 ± 299.8 μmol/L, and 95.7% of patients had stage 3 acute kidney injury (AKI). Drug-induced tubulointerstitial nephritis (TIN) was the most common cause (65.2%) of AKD, followed by severe nephrotic syndrome (17.4%). All patients had pathological changes indicating TIN, and 11 patients were complicated with the newly emerging glomerular disease (GD). The risk of oxalosis caused by increased enterogenous oxalate absorption accounted for only 26.1%, and others came from new kidney diseases. The majority (75%) of abundant (medium to severe) oxalosis occurred in patients without GD. There were no significant differences in the score for tubular injury (T-IS) and interstitial inflammation with different severities of oxalosis. Rate of Scr decrease (ΔScr%) at 2 weeks was negatively correlated with the severity of oxalosis ( = -0.542,  = 0.037), score for T-IS ( = -0.553,  = 0.033), and age ( = -0.736,  = 0.002). The decrease in Scr at 4 weeks was correlated with T-IS ( = -0.433), but had no correlation with oxalosis.

Conclusions: The present findings revealed that 95.7% of AKD with secondary renal oxalosis occurred in critically ill patients. AKD from tubular injury was the prominent cause. Severe oxalosis contributed to delayed early recovery of AKD.
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http://dx.doi.org/10.1080/0886022X.2021.1885443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939555PMC
December 2021

Evaluation of the Oxford classification in immunoglobulin A vasculitis with nephritis: a cohort study and meta-analysis.

Clin Kidney J 2021 Feb 11;14(2):516-525. Epub 2020 Aug 11.

Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.

Background: Similarities in clinicopathological presentations in immunoglobulin A (IgA) nephropathy and IgA vasculitis with nephritis (IgAVN) raise the question of the utility of the Oxford classification in the latter. The aim of this study was to evaluate the Oxford classification in IgAVN.

Methods: We conducted a retrospective cohort study and meta-analysis following systematic searching of the MEDLINE and Excerpta Medica Database (EMBASE) databases between January 2009 and September 2019. We modeled the association of 30 and 50% decline in estimated glomerular filtration rate or end-stage renal disease with pathologic lesions of the Oxford classification including mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), interstitial fibrosis/tubular atrophy (T) and crescents (C). Results were pooled using random-effects meta-analysis.

Results: The cohort study included 132 patients, and only T lesion was an independently risk factor in IgAVN. The meta-analysis yielded six retrospective studies with 721 patients and 139 endpoints. In multivariate model, T lesion was significantly associated with renal outcome (hazard ratio = 2.45, P = 0.007). M and C lesions could not predict renal outcome without evidence of heterogeneity. E and S lesions could not predict renal outcome with evidence of heterogeneity ( = 66.6%; P = 0.01, and = 65.8%; P = 0.03, respectively). Subgroup analysis showed that the possible reasons to the heterogeneity were from usage of immunosuppressant, sample size and follow-up time.

Conclusions: The study suggests that the Oxford classification could not be fully validated in IgAVN. Higher portion of immunosuppressant especially before renal biopsy might be the main confounder for the predictive value of Oxford classification in IgAVN.
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http://dx.doi.org/10.1093/ckj/sfaa129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886544PMC
February 2021

C3 glomerulonephritis along with light chain proximal tubulopathy without crystal deposits in multiple myeloma: a case report.

World J Surg Oncol 2021 Jan 22;19(1):24. Epub 2021 Jan 22.

Department of Hematology, Peking University First Hospital, No.8 Xi Shi Ku Street, Xi ChengDistrict, Beijing, 100034, China.

Background: Multiple myeloma causes different types of renal injury. C3 glomerulonephritis (C3GN) is characterised by an abnormal deposition of complement C3 in the glomeruli due to abnormal activation of the alternative pathway of the complement system. While the association between C3GN and multiple myeloma has been well established, mild renal injury by C3GN in multiple myeloma patients with high levels of light chain has not been reported.

Case Presentation: A 55-year-old Chinese man presented with proteinuria. Combined with immunofixation electrophoresis, bone marrow biopsy, and renal biopsy, he was diagnosed with IgA-type multiple myeloma accompanied by C3GN and light chain proximal tubulopathy without crystal deposits. Although he had a higher level of lambda serum-free light chain, the renal injury in this patient was mild. After treatment with four courses of BD, one course of PAD, and autologous stem cell transplantation, he achieved a very good partial hematologic response with stable renal function.

Conclusions: In multiple myeloma, the light chain reaches a certain level and persists, resulting in C3GN renal impairment. Early diagnosis and early intensive treatment are critical for the prognosis of such patients.
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http://dx.doi.org/10.1186/s12957-021-02135-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824921PMC
January 2021

Acute Kidney Injury Relevant to Tubulointerstitial Nephritis with Late-Onset Uveitis Superimposed by Thrombotic Microangiopathy: A Case Report and Review of the Literature.

Kidney Dis (Basel) 2020 Nov 20;6(6):414-421. Epub 2020 May 20.

Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.

Background: The syndrome of tubulointerstitial nephritis and uveitis (TINU) is an uncommon and multisystemic autoimmune disorder. This review reports a rare case of TINU being superimposed on thrombotic microangiopathy (TMA) and, by comparing with the available literature, also summarizes the clinical features, associated conditions, treatment, and outcome of patients with TINU.

Summary: Herein, we report the case of a 37-year-old male patient with acute kidney injury (AKI) clinicopathologically identified as malignant hypertension-induced TMA superimposed by acute tubulointerstitial nephritis, which was suspected to be related to drug hypersensitivity. After treatment with oral prednisone combined with a renin-angiotensin system inhibitor, the patient achieved partial renal recovery and was withdrawn from hemodialysis. Recurrent AKI concomitant with new-onset asymptomatic uveitis was detected during routine clinical follow-up after cessation of prednisone. TINU was then diagnosed, and prednisone followed by cyclophosphamide was prescribed. The patient achieved better renal recovery than in the first round of treatment and maintained stable renal function afterward. By reviewing the literature, 36 cases were reported as TINU superimposed on other conditions, including thyroiditis, osteoarthropathy, and sarcoid-like noncaseating granulomas.

Key Messages: TINU could be complicated by many other conditions, among which TMA is very rare. When presented as AKI, kidney biopsy is important for differential diagnosis. The case also shows that recurrent AKI with concomitant uveitis after prednisone withdrawal strongly suggested the need for long-term follow-up and elongated prednisone therapy for TINU syndrome.
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http://dx.doi.org/10.1159/000507668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706514PMC
November 2020
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