Renal damage and old age: risk factors for thrombosis in patients with ANCA-associated vasculitis.

INTRODUCTION: Thrombosis in ANCA-associated vasculitis (AAV) was prevalent and has been neglected in Chinese patients. This study tried to describe the clinical characteristics, identify the risk factors, and investigate the causal relationship between AAV and venous thromboembolism (VTE) by two-sample Mendelian randomization (MR) analysis. METHODS: In this retrospective, observational study, we included all hospitalized AAV patients from Jan 2013 to Apr 2022 in Peking Union Medical College Hospital. We collected their clinical data for multivariate regression analysis to determine the risk factors for thrombosis. The nomogram was constructed by applying these risk factors to predict thrombosis in AAV patients. As for MR analysis, we selected single nucleotide polymorphisms (SNPs) related to AAV from published genome-wide association studies and extracted the outcome data containing deep vein thrombosis (DVT) and pulmonary embolism (PE) from the UK biobank. RESULTS: 1203 primary AAV patients were enrolled, and thrombosis occurred in 11.3%. Multivariate regression suggested that older than 65 years, EGPA, neurological involvement, lung involvement, significantly elevated serum creatinine (> 500µmol/L), and elevated D-dimer were associated with thrombosis in AAV patients. The model demonstrated satisfied discrimination with an AUC of 0.769 (95% CI, 0.726-0.812). MR analysis showed that EGPA could increase the risk of developing DVT and PE (OR = 1.0038, 95%CI = 1.0035-1.0041, P = 0.009). CONCLUSION: Thrombosis was not rare in Chinese patients with AAV. Renal damage and old age emerged as critical risk factors for thrombosis. EGPA might have a potential causal relationship with DVT and PE.

Rare renal proximal tubular dysfunctions in primary biliary cholangitis.

INTRODUCTION: Renal involvement of primary biliary cholangitis (PBC) usually presents as distal renal tubular acidosis. Proximal tubular (PT) dysfunctions in PBC were rarely reported with unclear clinicopathological characteristics and renal prognosis. METHODS: We identified 11 cases of PBC with PT dysfunctions (PBC-PT). Their medical document, kidney pathology, and follow-up data were retrospectively reviewed and analyzed. RESULTS: The 11 PBC-PT patients were mainly middle-aged (57.8 ± 5.2 years) females (81.8%). Most of them were asymptomatic PBC (7, 63.6%) with a high prevalence of elevated serum immunoglobulin M (IgM, 81.8%) and G (IgG, 54.5%) levels. In the kidney, they had a mean estimated glomerular filtration rate (eGFR) level of 46.54 ± 23.03 ml/min/1.73m2, and 81.8% of them had eGFR below 60 ml/min/1.73m2. They showed different degrees of PT dysfunctions, including hyperuricosuria, hypouricemia, normoglycemic glycosuria, generalized aminoaciduria, hyperphosphaturia, and hypophosphatemia. Their kidney pathology showed tubulointerstitial nephritis with lymphoplasmacytic infiltrates, brush border defects, and proximal tubulitis. After glucocorticoids treatment, the PT dysfunctions manifesting as hypophosphatemia, hypouricemia, and renal glycosuria all recovered, and the eGFR levels were improved from 43.24 ± 19.60 ml/min/1.73m2 to 55.02 ± 21.14 ml/min/1.73m2 (p = 0.028), accompanied by significant improvements of serum IgM levels (from 5.97 ± 4.55 g/L to 2.09 ± 1.48 g/L, p = 0.019). CONCLUSIONS: The PT dysfunctions were rare in PBC patients, and glucocorticoids treatment could benefit the improvements of eGFR and tubular functions.

Renal Outcomes in Older Adults with Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis: A New Prediction Model.

INTRODUCTION: Older patients with antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) commonly experience renal impairment and poor prognoses. This study aimed to establish a risk-scoring system for predicting composite renal outcomes in older patients with AAV. METHODS: This retrospective observational study included all patients with AAV hospitalized in a single-center tertiary hospital in China between January 2013 and April 2022. Patients aged ≥65 years were defined as older adults and short-term composite renal outcomes included a ≥25% reduction in estimated glomerular filtration rate (eGFR) (for AKI), renal replacement therapy, provision of renal replacement therapy (long-term dialysis, kidney transplant, or sustained eGFR <15 mL/min/1.73 m), or all-cause mortality. Patients were randomly divided into development and validation cohorts (2:1). Logistic regression analysis was performed in the development cohort to analyze risk factors. The scoring system was established accordingly and further validated in the validation cohort. RESULTS: 1,203 patients were enrolled in the study, among whom the older adult group accounted for 36% with a mean age of 71. The older adult group had a worse prognosis, a higher mortality rate, a higher rate of end-stage renal disease, and worsening renal function. Logistic regression showed that age >75 years, chronic heart disease, and elevated serum creatinine and D-dimer values were risk factors for poor prognosis in patients with AAV. The development and validation cohorts in patients with AAV produced area under the curve values of 0.82 (0.78-0.86) and 0.83 (0.77-0.89), respectively. CONCLUSION: We established a risk-scoring system based on baseline clinical characteristics to predict composite renal outcomes in patients with AAV. Our results suggest that more attention should be paid to older patients with severe renal impairment and active inflammation.

[Palliative Care for End-Stage Renal Disease:A Case Report and Literature Review].

Since end-stage renal disease leads to a variety of problems such as disability,reduced quality of life,and mental and psychological disorders,it has become a serious public health problem around the globe.Renal palliative care integrates palliative care philosophy in the care for patients with end-stage renal disease.As a planned,comprehensive,patient-centered care,renal palliative care focuses on the patient's symptoms and needs,aiming to reduce the suffering throughout the course of the disease,including but not limited to end-of-life care.This study reports the palliative care practice for a patient on maintenance dialysis in the Blood Purification Center of Peking Union Medical College Hospital and reviews the present situation of palliative care in end-stage renal disease.

The spectrum of kidney biopsy findings in Chinese HIV-infected patients.

OBJECTIVES: HIV-associated kidney disease is common but data on the pathology spectrum of kidney biopsy in China is lacking. This study aimed to illustrate the clinical presentation, laboratory findings and pathological spectrum of different subtypes of HIV-associated kidney disease in China. METHODS: Eighteen HIV patients with renal biopsy indications at the Peking Union Medical College Hospital from January 2002 to October 2021 were retrospectively enrolled. All had CD4 counts and HIV viral load measurements. Renal biopsies were examined with light microscopy, immunofluorescence, and electron microscopy. Shapiro-Wilk test was used to test whether the data was normally distributed. The data is presented as medians (interquartile range), number (%), or means (±SD) according to their distribution. RESULTS: Seventeen patients had glomerular disease, and one patient had interstitial nephritis. Membranous nephropathy was present in eight patients (47.1%), and IgA nephropathy in four patients (23.5%). The difference in urine protein and serum albumin before and after treatment was statistically significant and no deaths or dialysis were observed to the end of follow-up. CONCLUSION: This study found that classic HIV-associated nephropathy (HIVAN) was uncommon in Chinese HIV patients. HIV immune complex kidney (HIVICK) disease, such as membranous or IgA nephropathy, was more common, and associated with better prognosis. Antiretroviral therapy, ACE inhibitors, and angiotensin II receptor blockers were effective in decreasing proteinuria and preserving renal function. The use of corticosteroids and immunosuppressive agents seems safe. However, the nephrotoxic effect of antiretroviral agents and other medications should be carefully monitored.

Development and validation of a prediction model for glucocorticoid-associated osteonecrosis of the femoral head by targeted sequencing.

OBJECTIVE: To develop and validate a prediction model based on targeted sequencing for glucocorticoid (GC)-associated osteonecrosis of the femoral head (GA-ONFH) in GC-treated adults. METHODS: This two-centre retrospective study was conducted between July 2015 and April 2019 at Zhongshan Hospital (training set) and the Sixth People's Hospital (test set) in Shanghai, China. All patients had a history of GC therapy, with a dose exceeding 2000 mg equivalent prednisone within 6 weeks. Patients were divided into two groups according to whether they were diagnosed with GA-ONFH within 2 years after GC initiation. Blood or saliva samples were collected for targeted sequencing of 358 single nucleotide polymorphisms and genetic risk score (GRS) calculating for developing GA-ONFH prediction model. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were performed to evaluate and validate the model. RESULTS: . The training set comprised 117 patients, while the test set comprised 30 patients for external validation. Logistic regression analysis showed that GRS was significantly associated with GA-ONFH (OR 1.87, 95% CI: 1.48, 2.37). The ROC and DCA curves showed that the multivariate model considering GRS, age at GC initial, sex and underlying diseases had a discrimination with area under the ROC curve (AUC) of 0.98 (95% CI: 0.96, 1.00). This model was further externally validated using the test set with an AUC of 0.91 (95% CI: 0.81, 1.00). CONCLUSION: Our prediction model comprising GRS, age, sex and underlying diseases yields valid predictions of GA-ONFH incidence. It may facilitate effective screening and prevention strategies of GA-ONFH.

Diffusion kurtosis imaging as an imaging biomarker for predicting prognosis in chronic kidney disease patients.

BACKGROUND: Renal fibrosis is the strongest prognostic predictor of end-stage renal disease (ESRD) in chronic kidney disease (CKD). Diffusion kurtosis imaging (DKI) is a promising method of magnetic resonance imaging successfully used to assess renal fibrosis in immunoglobulin A nephropathy. This study aimed to be the first to evaluate the long-term prognostic value of DKI in CKD patients. METHODS: Forty-two patients with CKD were prospectively enrolled, and underwent DKI on a clinical 3T MR scanner. We excluded patients with comorbidities that could affect the volume or the components of the kidney. DKI parameters, including mean Kurtosis (K), mean diffusivity and apparent diffusion coefficient (ADC) of kidney cortex were obtained by region-of-interest measurement. We followed up these patients for a median of 43 months and investigated the correlations between each DKI parameter and overall renal prognosis. RESULTS: Both K and ADC values were correlated well with the estimated glomerular filtration rate (eGFR) on recruitment and the eGFR of the last visit in follow-up (P ˂ 0.001). K and ADC values were also well associated with the eGFR slopes in CKD patients, both with the first-last time point slope (P = 0.011 and P ˂ 0.001, respectively) and with the regression slope (P = 0.010 and P ˂ 0.001, respectively). Cox proportional hazard regression indicated that lower eGFR and ADC values independently predicted eGFR loss of ˃30% and ESRD. The receiver operating characteristic analysis showed that K and ADC values were predictable for renal prognosis, and ADC displayed better capabilities for both ESRD [area under the curve (AUC) 0.936, sensitivity 92.31%, specificity 82.76%] and the composite endpoint (eGFR loss ˃30% or ESRD) (AUC 0.881, sensitivity 66.67%, specificity 96.3%). CONCLUSIONS: Renal ADC values obtained from DKI showed significant predictive value for the prognosis of CKD patients, which could be a promising noninvasive technique in follow-up.

Identification of biomarkers, immune infiltration landscape, and treatment targets of ischemia-reperfusion acute kidney injury at an early stage by bioinformatics methods.

BACKGROUND: Mechanisms underlying ischemia/reperfusion injury-acute kidney injury (IRI-AKI) are not fully elucidated. We conducted an integrative analysis of IRI-AKI by bioinformatics methods. METHODS: We screened gene expression profiles of the IRI-AKI at early phase from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified and enrichment pathways were conducted based on gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and Gene set enrichment analysis (GSEA). Immune cell infiltration analysis was performed to reveal the change of the microenvironment cell types. We constructed protein-protein interaction (PPI), and Cytoscape with plug-ins to find hub genes and modules. We performed robust rank aggregation (RRA) to combine DEGs and analyzed the target genes for miRNA/transcription factor (TF) and drug-gene interaction networks. RESULTS: A total of 239 and 384 DEGs were identified in GSE87024 and GSE34351 separately, with the 73 common DEGs. Enrichment analysis revealed that the significant pathways involve mitogen-activated protein kinase (MAPK) signaling, interleukin-17, and tumor necrosis factor (TNF) signaling pathway, etc. RRA analysis detected a total of 27 common DEGs. Immune cell infiltration analysis showed the plasma cells reduced and T cells increased in IRI-AKI. We identified JUN, ATF3, FOS, EGR1, HMOX1, DDIT3, JUNB, NFKBIZ, PPP1R15A, CXCL1, ATF4, and HSPA1B as hub genes. The target genes interacted with 23 miRNAs and 116 drugs or molecular compounds such as curcumin, staurosporine, and deferoxamine. CONCLUSION: Our study first focused on the early IRI-AKI adopting RRA analysis to combine DEGs in different datasets. We identified significant biomarkers and crucial pathways involved in IRI-AKI and first construct the immune landscape and detected the potential therapeutic targets of the IRI-AKI by drug-gene network.

Optimal targets of chronic kidney disease-mineral and bone disorder markers for Chinese patients with maintenance peritoneal dialysis: a single-center retrospective cohort study.

BACKGROUND: The chronic kidney disease-mineral and bone disorder（CKD-MBD) is known to be associated with increased mortality in dialysis patients, but whether current global guidelines for CKD-MBD, which were primarily developed from hemodialysis, are suitable for peritoneal dialysis (PD) patients practice require further investigation. METHODS: This is a single-center retrospective cohort study. In total 491 prevalent PD patients (median follow-ups: 34 months) from Peking Union Medical College Hospital (PUMCH) from January 2004 to December 2017 were included and followed until 30 June 2018. In the first dialysis year, the average levels of serum calcium, albumin-corrected calcium (CorCa), phosphorus, and parathyroid hormone (PTH) levels were the interested predictors in Cox proportional regression model. RESULTS: Of these PD patients (age 58 ± 17 years), 52% were male and 36% had diabetic nephropathy. In Cox regression over first-year mean parameters, PTH <100 pg/mL (HR = 1.97, 95% CI 1.32 to 2.94, p < 0.001) and ≥300 pg/mL (HR = 2.24, 95% CI 1.32 to 3.81, p = 0.003) were associated with increased all-cause mortality than that of PTH 100-200 pg/mL. Patients with albumin-corrected serum calcium level < 2.13 mmol/L also had higher risk of death than patients with level of 2.13 to 2.38 mmol/L (HR = 2.06, 95% CI 1.06 to 4.01, p = 0.02). Serum phosphorus ≥1.45 mmol/L were associated with increased all-cause mortality. However, lacking of data on 25-hydroxy vitamin D, alkaline phosphatase, and activated vitamin-D are limitations of our analysis. CONCLUSIONS: As one of the largest PD cohort study focusing on CKD-MBD, we demonstrated that the level of CKD-MBD markers in the first PD year are independent predictors of all-cause mortality. PTH 100-300 pg/mL might be the best target for Chinese PD patients.

[Nephrotic Syndrome Caused by AA Amyloidosis Secondary to Unicentric Castleman's Disease:Report of One Case].

AA amyloidosis is a rare systemic complication caused commonly by chronic inflammatory arthritis,periodic fever disease,vasculitis,tumors,etc.Castleman's disease is an uncommon cause of AA amyloidosis.Here,we reported a case of unicentric Castleman's disease-induced AA amyloidosis with nephrotic syndrome as the main manifestation.The laboratory examination showed elevated levels of inflammatory indicators.We summarized the clinical manifestations,diagnosis,and therapy of this case,aiming to facilitate the management of patients with unknown reasons of renal amyloidosis.

Continuous hypergammaglobulinemia and proteinuria after the recovery of the visceral Leishmaniasis: a case report.

BACKGROUND: Kidney involvement of visceral Leishmaniasis is previously reported, but knowledge is limited. Hypergammaglobulinemia is common in visceral leishmaniasis patients. Whether hypergammaglobulinemia after leishmaniasis depletion can cause kidney injury is not well reported yet. CASE PRESENTATION: We reported a patient who recovered from visceral Leishmaniasis but showed persistent hypergammaglobulinemia and elevated urinary protein. Kidney biopsy showed glomerular hypertrophy with mild segmental mesangial proliferation without tubulointerstitial involvement in light microscopy. No immune complex deposit was found in the mesangial area by neither immunofluorescent staining nor electronic microscope. Increased lysosomes were observed in proximal tubules by electronic microscope. Valsartan was administered to decrease urinary protein, and no immune-suppressive therapy was added. The urinary protein and serum IgG level gradually dropped, and serum creatinine level remained stable during three- month follow up. CONCLUSIONS: Hypergammaglobulinemia is unlikely to cause renal structural or functional damage in the short term. Angiotensin blockade significantly reduced urine protein, with a minor effect on IgG elimination.

Double-filtration plasmapheresis combined with immunosuppressive treatment for severe pemphigus: 10 years' experience of a single center in China.

BACKGROUND: Pemphigus is a group of rare and severe autoimmune blistering disease mediated by pathogenic autoantibodies against desmogleins. Plasmapheresis can directly remove autoantibodies from circulation, which has been applied to the treatment of pemphigus as an adjuvant therapy. But the results of the researches are controversial. This study aims to evaluate the efficacy and safety of double filtration plasmapheresis (DFPP) combined with immunosuppressive treatment for patients with severe pemphigus in our single center. METHODS: We retrospectively analyzed 17 patients with severe pemphigus who were unresponsive to high-dose corticosteroid and received DFPP treatment between January 2010 and January 2020. The information on demographic characteristics, clinical and laboratory data, treatment regimens, and clinical outcomes were collected. RESULTS: All the patients were diagnosed as severe pemphigus and had a period of at least 1 week of high-dose prednisone (1-1.5 mg/kg/day), but they were unresponsive to corticosteroid and immunosuppressants treatment. They received DFPP treatment as an adjuvant therapy. After DFPP treatment, the titers of desmogleins antibodies significantly decreased (P < .001), Nikolsky's sign became negative and no new blisters appeared. The dosage of corticosteroid could begin to taper down rapidly in 9 ± 4 days. On discharge, the dosage of prednisone decreased significantly (51 ± 3 mg/day, P < .001). No major adverse events happened that could lead to the termination of DFPP treatment. CONCLUSION: Double filtration plasmapheresis combined with immunosuppressive treatment is an effective and safe therapeutic regimen for severe pemphigus. DFPP can also contribute to the dosage reduction of steroid to avoid more drug-related side effect.

Long-term ambient PM2.5 exposure associated with cardiovascular risk factors in Chinese less educated population.

INTRODUCTION: Long-term exposure to ambient air pollution is related to major cardiovascular risk factors including diabetes, hypertension, hyperlipidemia and overweight, but with few studies in high-concentration nations like China so far. We aimed to investigate the association between long-term exposure to ambient fine particulate matter (particles with an aerodynamic diameter ≤ 2.5 µm, PM2.5) and major cardiovascular risk factors in China. METHODS: Adult participants with selected biochemical tests were recruited from the Chinese Physiological Constant and Health Condition (CPCHC) survey conducted from 2007 to 2011. Gridded PM2.5 data used were derived from satellite-observed data with adjustment of ground-observed data. District-level PM2.5 data were generated to estimate the association using multivariate logistic regression model and generalized additive model. RESULTS: A total of 19,236 participants from the CPCHC survey were included with an average age of 42.8 ± 16.1 years, of which nearly half were male (47.0%). The annual average PM2.5 exposure before the CPCHC survey was 33.4 (14.8-53.4) µg/m3, ranging from 8.0 µg/m3 (Xiwuqi) to 94.7 µg/m3 (Chengdu). Elevated PM2.5 was associated with increased prevalence of hypertension (odds ratio (OR) =1.022, 95% confidence interval (95%CI): 1.001, 1.043) and decreased prevalence of overweight (OR = 0.926, 95%CI: 0.910, 0.942). Education significantly interacted with PM2.5 in association with all the interesting risk factors. Each 10 µg/m3 increment of PM2.5 was associated with increased prevalence of diabetes (OR = 1.118, 95%CI: 1.037, 1.206), hypertension (OR = 1.101, 95%CI: 1.056, 1.147), overweight (OR = 1.071, 95%CI: 1.030, 1.114) in participants with poor education, but not in well-educated population. PM2.5 exposure was negatively associated with hyperlipidemia in all participants (OR = 0.939, 95%CI: 0.921, 0.957). The results were robust in all the sensitivity analyses. CONCLUSION: Association between long-term PM2.5 exposure and cardiovascular risk factors might be modified by education. PM2.5 was associated with a higher prevalence of diabetes, hypertension, and overweight in a less-educated population with time-expose dependency. Long-term exposure to PM2.5 might be associated with a lower prevalence of hyperlipidemia.

Clinicopathological Features and Outcomes of Acute Kidney Injury in Critically Ill COVID-19 with Prolonged Disease Course: A Retrospective Cohort.

BACKGROUND: The incidence, severity, and outcomes of AKI in COVID-19 varied in different reports. In patients critically ill with COVID-19, the clinicopathologic characteristics of AKI have not been described in detail. METHODS: This is a retrospective cohort study of 81 patients critically ill with COVID-19 in an intensive care unit. The incidence, etiologies, and outcomes of AKI were analyzed. Pathologic studies were performed in kidney tissues from ten deceased patients with AKI. RESULTS: A total of 41 (50.6%) patients experienced AKI in this study. The median time from illness to AKI was 21.0 (IQR, 9.5-26.0) days. The proportion of Kidney Disease Improving Global Outcomes (KDIGO) stage 1, stage 2, and stage 3 AKI were 26.8%, 31.7%, and 41.5%, respectively. The leading causes of AKI included septic shock (25 of 41, 61.0%), volume insufficiency (eight of 41, 19.5%), and adverse drug effects (five of 41, 12.2%). The risk factors for AKI included age (per 10 years) (HR, 1.83; 95% CI, 1.24 to 2.69; P=0.002) and serum IL-6 level (HR, 1.83; 95% CI, 1.23 to 2.73; P=0.003). KDIGO stage 3 AKI predicted death. Other potential risk factors for death included male sex, elevated D-dimer, serum IL-6 level, and higher Sequential Organ Failure Assessment score. The predominant pathologic finding was acute tubular injury. Nucleic acid tests and immunohistochemistry failed to detect the virus in kidney tissues. CONCLUSIONS: AKI was a common and multifactorial complication in patients critically ill with COVID-19 at the late stage of the disease course. The predominant pathologic finding was acute tubular injury. Older age and higher serum IL-6 level were risk factors of AKI, and KDIGO stage 3 AKI independently predicted death.

Divergence between serum creatine and cystatin C in estimating glomerular filtration rate of critically ill COVID-19 patients.

BACKGROUND: The clinical use of serum creatine (sCr) and cystatin C (CysC) in kidney function evaluation of critically ill patients has been in continuous discussion. The difference between estimated glomerular filtration rate calculated by sCr (eGFRcr) and CysC (eGFRcysc) of critically ill COVID-19 patients were investigated in this study. METHODS: This is a retrospective, single-center study of critically ill patients with COVID-19 admitted in intensive care unit (ICU) at Wuhan, China. Control cases were moderate COVID-19 patients matched in age and sex at a ratio of 1:1. The eGFRcr and eGFRcysc were compared. The association between eGFR and death were analyzed in critically ill cases. The potential factors influencing the divergence between eGFRcr and eGFRcysc were explored. RESULTS: A total of 76 critically ill COVID-19 patients were concluded. The mean age was 64.5 ± 9.3 years. The eGFRcr (85.45 (IQR 60.58-99.23) ml/min/1.73m2) were much higher than eGFRcysc (60.6 (IQR 34.75-79.06) ml/min/1.73m2) at ICU admission. About 50 % of them showed eGFRcysc < 60 ml/min/1.73 m2 while 25% showed eGFRcr < 60 ml/min/1.73 m2 (χ2 = 10.133, p = 0.001). This divergence was not observed in moderate group. The potential factors influencing the divergence included serum interleukin-6 (IL-6), tumor necrosis factor (TNF-α) level as well as APACHEII, SOFA scores. Reduced eGFRcr (<60 mL/min/1.73 m2) was associated with death (HR = 1.939, 95%CI 1.078-3.489, p = 0.027). CONCLUSIONS: The eGFRcr was generally higher than eGFRcysc in critically ill COVID-19 cases with severe inflammatory state. The divergence might be affected by inflammatory condition and illness severity. Reduced eGFRcr predicted in-hospital death. In these patients, we advocate for caution when using eGFRcysc.

Acute Kidney Injury Caused by TAFRO Syndrome in a Chinese Patient: Efficacy of Long-Term Corticosteroids Combined with Bortezomib and Cyclophosphamide.

INTRODUCTION: Thrombocytopenia, ascites, myelofibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome is a newly recognized and rare clinical subtype of Castleman disease. Renal involvement in TAFRO syndrome usually presents with mild proteinuria, microscopic hematuria, and acute renal injury requiring temporary renal replacement. There is no standard therapy available and treatment failures are common, leading to a poor prognosis. We report a case of acute renal failure caused by TAFRO syndrome, successfully managed by long-term corticosteroids combined with bortezomib and cyclophosphamide. CASE PRESENTATION: The patient was a 52-year-old female who presented with fever, anasarca, oliguria, and abdominal distension at first. She progressed rapidly to anuric renal failure requiring hemodialysis. She also demonstrated thrombocytopenia, anemia, coagulopathy, and a hyperinflammatory status. Her CT scan showed severe polyserositis, splenomegaly, and lymphadenopathy. Her serum vascular epithelial growth factor level was significantly elevated. Axillary lymph node biopsy showed hyaline-vascular type Castleman disease, supporting the diagnosis of TAFRO syndrome. Her renal function recovered after high-dose steroids and supportive treatment. A weekly dosing regimen of bortezomib, cyclophosphamide, and dexamethasone combined with medium dose prednisone in between were deployed. Her blood cell count and renal function remained stable after 6 months. The inflammation was suppressed and the polyserositis resolved completely. CONCLUSION: TAFRO syndrome is rare and has a poor prognosis due to the lack of standard treatment. Our patient might be the first TAFRO case successfully treated by bortezomib, cyclophosphamide, and corticosteroids.

Clinical and laboratory features of female Gitelman syndrome and the pregnancy outcomes in a Chinese cohort.

AIM: Gitelman syndrome (GS) is a rare inherited salt-losing renal tubulopathy. Data on clinical features and the pregnancy outcome for female GS patients in a large cohort are lacking. The study was aimed to explore the phenotype and pregnant issue for female GS patients. METHODS: GS cases from the National Rare Diseases Registry System of China (NRSC) were collected, and detailed clinical, laboratory and genetic data were analysed. Articles on pregnancy in GS were also systemically reviewed. RESULTS: A total of 101 GS patients were included; among them, 42.6% were female and 79.2% showed hypomagnesaemia. A lower proportion of female patients presented before 18 years of age, with less frequently reported polyuria, higher serum potassium and less urine sodium and chloride excretions. There was no gender difference in the sodium-chloride cotransporter (NCC) dysfunction evaluated by hydrochlorothiazide test. Twelve of the 43 female GS patients delivered after disease symptom onset, and their pregnancies were generally uneventful. As a group, pregnant GS patients had lower potassium levels in the first-trimester (P = .002) requiring higher potassium supplementation. After delivery, serum potassium (P = .02) and magnesium (P = .03) increased significantly. Both caesarean section and vaginal delivery were safe. CONCLUSION: Female GS patients may have a less severe phenotype with generally favourable outcomes of pregnancy. Intensive monitoring and increased potassium supplementation are necessary during pregnancy, especially in the first-trimester.

Early-start and conventional-start peritoneal dialysis: a Chinese cohort study on outcome.

Background: Early-start peritoneal dialysis (PD) is an effective option for patients need unplanned dialysis. However, there are few studies on the long-term prognosis of early-start PD patients.Methods: In this retrospective study, 635 eligible patients from 1 March 1996 to 30 September 2016 were included, and divided into three groups according to the duration of break-in period: 3 days or less, 4-13 days and more than 14 days. Patients started PD within 2 weeks and after 2 weeks were defined as early-start and conventional-start, respectively. The primary outcome was all-cause mortality, and the secondary outcome measures were peritonitis free survival and technical survival. Mechanical and infectious complications in the first 180 days were also analyzed.Results: Early-start PD patients were more likely to have higher serum total carbon dioxide and creatinine levels and lower serum albumin, Kt/v, creatinine clearance (Ccr) and residual glomerular filtration rate (rGFR) levels at the start of PD. The median follow-up period was 30 months (interquartile range, 13-53 months). A worse survival was observed in the early-start group than that in the conventional-start group (p < 0.001), even adjustment for the covariates (HR 1.549, 95%CI 1.104-2.173, p = 0.011). In the subgroup analysis, in patients commencing PD after 2006 early-start and conventional-start PD patients had comparable survival. No differences were observed in the rate of infectious and mechanical complications, peritonitis-free survival and technique survival between early-start and conventional-start PD patients.Conclusions: Early-start PD could be a safe and effective strategy for patients needing unplanned dialysis initiation with the progress of technology on PD.

Clinical significance of C4d deposition in renal tissues from patients with primary Sjögren's syndrome-a preliminary study.

BACKGROUND: To evaluate renal expression of C4d, a complement component in the classical/mannose binding lectin (MBL) pathway, in patients with primary Sjögren's syndrome (pSS)-associated renal impairments. METHODS: We retrospectively reviewed the clinical and pathological data from 39 patients with pSS presenting with renal impairments. C4d was examined in paraffin-embedded biopsy tissues using immunohistochemistry. Glomerular C4d positive was defined when > 75% glomeruli were globally stained. Tubulointerstitial C4d (TI-C4d) were scored semi-quantitatively as 0 (absent), 1 (spotty or weak), 2 (patchy) and 3 (diffuse). A TI-C4d score ≥ 2 was considered TI-C4d positive and included in the TI-C4d+ group and vice versa. Peritubular capillary (PTC) C4d was scored as 0 (absent), 1 (0~10%, minimal), 2 (10%~ 50%, focal), and 3 (> 50%, diffuse). RESULTS: Glomerular C4d deposition was observed in all 8 patients with pSS-related membranous nephropathy (MN) without obvious C1q deposition. Two of 5 patients with mesangial proliferative glomerulonephritis and 1 of 2 patients with IgA nephropathy had mild mesangial C4d deposition. Sixteen patients (6 glomerular dominant and 10 tubulointerstitial dominant) presented TI-C4d score ≥ 2. Patients in the TI-C4d+ group exhibited a higher serum creatinine level at the time of renal biopsy (TI-C4d+ 132.5 [89.7, 165.5] vs. TI-C4d- 83.0 [70.7, 102.0] µmol/L, P = 0.008). PTC C4d was observed in 12 patients, with each of minimal, focal and diffuse staining being noted in 4 patients. CONCLUSIONS: The MBL pathway of complement activation was potentially involved in pSS-related MN. Tubulointerstitial C4d might be a pathological marker of severe renal injury in patients with pSS-related renal impairments.

Gender and chronic kidney disease in ankylosing spondylitis: a single-center retrospectively study.

BACKGROUND: Ankylosing spondylitis (AS) is a well-known male-predominant inflammatory disease. This study aimed to assess the gender disparity in chronic kidney disease (CKD) in AS patients in China. METHODS: AS patients were retrospectively studied at Peking Union Medical College hospital between January 2002 and June 2018. RESULTS: Among 616 patients with AS, 154 (25.0%) patients had CKD (age, 41.8 ± 14.2 years; male:female, 3.2:1). Overall, 80 (13.0%) patients had only microscopic hematuria, 62 (10.1%) had proteinuria with or without hematuria, and 33 (5.4%) exhibited a reduced estimated glomerular filtration rate (eGFR, ≤60 mL/min/1.73 m2). Male CKD patients had more frequent proteinuria (p < 0.01), less microscopic hematuria only (p < 0.01), and lower eGFR (p = 0.04) compared with females. CKD was independently associated with hyperuricemia and total cholesterol in females, and with hyperuricemia, hypertension, and serum albumin in males. After follow-up for 1-7 years, five patients required renal replacement therapy including two patients who were already at stage 5 CKD when enrolled and three patients whose creatinine doubled. One patient died in the male group. No patients in the female group showed progression of renal dysfunction. CONCLUSIONS: CKD is a common comorbidity in patients with AS. Male patients are more likely to develop severe manifestations compared with female patients. Hyperuricemia was a strong independent risk factor for CKD in both genders, while hypertension and low serum albumin were risk factors for CKD only in males.