A 31-year-old man sought medical evaluation for a 2-year history of edema and proteinuria, with prior pathology suggesting atypical membranous nephropathy (MN). Despite treatment with a combination of steroids, calcineurin inhibitors, and four courses of rituximab (1 g, intravenous injection), the patient′s nephrotic syndrome showed no relief (24 h urine protein peaked at 31.18 g/d), indicating refractory nephrotic syndrome. Later in the disease course, a sudden surge of creatinine level (322.5 μmol/L) prompted a renal biopsy, which revealed concurrent acute interstitial nephritis. Further treatment involving steroids, cyclophosphamide, and a fifth rituximab infusion (1 g, intravenous injection) resulted in improvement in renal function (serum creatinine: 322.5?147 μmol/L), but the MN failed to achieve partial relief. Subsequent treatment with the novel humanized CD20 monoclonal antibody obinutuzumab (1 g, intravenous injection) was initiated. In the latest follow-up, anti-phospholipase-A2-receptor antibody (PLA2R) antibody were negative, B cells were eliminated, serum albumin was 36 g/L, urine protein-to-creatinine ratio was 4 810 mg/g, and serum creatinine was 162 μmol/L. This case underscores the potential efficacy of obinutuzumab in refractory MN. For advanced MN cases, prompt identification of the cause of acute kidney injury is crucial, emphasizing the need for targeted interventions to potentially stall renal function decline.

Primary biliary cirrhosis/cholangitis is an autoimmune disease. Renal tubular acidosis is a common form in PBC cases, but Fanconi syndrome is rarely reported. The paper reported a 66-year-old female patient with fatigue, renal insufficiency and elevated bile duct enzymes. The patient presented with type 2 proximal renal tubular acidosis and complete Fanconi syndrome. Laboratory examinations showed high-titer-positive anti-mitochondrial antibodies, elevated serum IgM, and type 3 cryoglobulinemia. Renal biopsy revealed interstitial nephritis, and electron micrographs showed abnormal mitochondria in proximal tubular epithelial cells. The patient's renal function ameliorated, and acid-base imbalance and electrolyte disturbances were corrected after high-dose glucocorticoid treatment.

The article reported one case of renal damage caused by lenvatinib in the treatment of advanced primary liver cancer. The patient was a 63-year-old male who was admitted to the hospital due to "liver cancer for 4 years, blood pressure elevation for nearly 2 years, and edema for 7 months". During the treatment of liver tumors with atezolizumab combined with lenvatinib, blood pressure increased and renal insufficiency aggravated progressively. Pathological light microscopy of renal biopsy showed endothelial cell lesion and tubulointerstitial damage, and electron microscopy showed moderate proliferation of mesangial cells and deposition of mesangial matrix. There were many agglomerated low-electron density deposits in the mesangial area, and a small amount of electron dense deposits in the subendothelium. The pathological diagnosis was endothelial cell disease (thrombotic microangiopathy) and secondary focal segmental glomerulosclerosis. Renal injury was considered as secondary to lenvatinib. After discontinuing lenvatinib and giving angiotensin receptor antagonist treatment, blood pressure was normal, urine protein turned negative, and renal function improved significantly after 8 months of outpatient follow-up.

Objective To prepare and identify rabbit anti-cyclin dependent kinase 6 (CDK6) antibody. Methods The recombinant pET21a (+)/CDK6 was successfully constructed, then the recombinant plasmid was transformed into E.coli BL21 (DE3) competent cells and was induced by isopropyl-β-D-thiogalactopyranoside (IPTG) for protein expression, which was detected by SDS-PAGE and Western blot analysis. The expressed protein was purified by nickel-chelating nitrilotriacetic acid (Ni-NTA) agarose and then analyzed by SDS-PAGE. Japanese white rabbits were immunized with purified CDK6 protein for many times every two weeks. The blood was collected at 0, 2, 4 and 6 weeks after immunization, and serum was separated from blood. The titer was detected by indirect ELISA. Western blot analysis, immunofluorescence assay and immunohistochemistry were employed to determine the specificity. Results High purity CDK6 protein and high specificity of rabbit anti-CDK6 antibody were successfully prepared. The titer of CDK6 rabbit serum antibody reached 1:30 000 after immunization, which could specifically recognize the CDK6 protein expressed in cervical cancer cell line and cervical cancer tissues. Conclusion The high titer and specificity of rabbit anti-CDK6 antibody is successfully prepared.
Animals ; Female ; Humans ; Rabbits ; Antibodies ; Antibody Specificity ; Blotting, Western ; Cyclin-Dependent Kinase 6 ; Enzyme-Linked Immunosorbent Assay ; Uterine Cervical Neoplasms

Objective:To analyze the clinical and pathological characteristics, treatment and prognosis of renal changes in patients with Kimura disease and improve the clinicians′ understanding on renal manifestations of Kimura disease.Methods:The clinical data of Kimura disease patients with definite diagnosis and detailed data in Peking Union Medical College Hospital from January 1980 to August 2020 were retrospectively analyzed. The patients were divided into renal impairment group and non-renal impairment group according to whether the kidney was involved or not and the related clinical data between the two groups were compared. The patients presenting with nephrotic syndrome were followed up.Results:There were 60 patients with Kimura disease confirmed by pathological diagnosis with 48 males. The median age was 33(3, 62) years old, and the median duration was 36(12, 111) months. There were 18 cases complicated with renal injury in 49 patients with complete routine urine and renal function examination and the main manifestations of renal injury were proteinuria and/or microscopic hematuria. There was no significant difference at age, sex and absolute value of eosinophils between the two groups (all P>0.05). Compared with the renal inpairment group, patients in non-renal inpairment group had longer course of disease, higher levels of hypersensitive C-reactive protein and erythrocyte sedimentation rate, and lower median values of total eosinophils and total IgE, but there was no statistically significant difference (all P>0.05). Among the patients with renal involvement, 6 patients met the diagnostic criteria for nephrotic syndrome, and 5 of them completed renal biopsies. The renal pathological diagnosis was membranous nephropathy in 2 cases and minimal change disease in 3 cases, and no interstitial eosinophil infiltration was found in renal biopsy tissues. These patients had a good response to glucocorticoids and/or immunosuppressive therapy, and achieved complete remission of nephrotic syndrome; at the same time, lymphadenopathy caused by Kimura disease could be well controlled. Conclusions:Kimura disease can combine with various renal lesions, and the pathology of nephrotic syndrome can be membranous nephropathy or minimal change nephropathy. After energetic treatment of glucocorticoids and/or immunosuppressive therapy, nephrotic syndrome can be completely relieved, and lymphadenopathy can be well controlled. The relationship between Kimura disease and renal disease needs further study.

A 65-year-old woman presented with intermittent right hand numbness and elevated serum creatinine for more than 2 months. The histological examination of kidney biopsy showed renal arterioles occlusion and interstitial fibrosis. Pathological abnormality was originally considered as a part of systemic atherosclerosis. Thus, rosuvastatin 20 mg/d, fosinopril 10 mg/d, metoprolol 47.5 mg/d and aspirin 0.1g/d were administrated. No improvement of renal function was seen. Further Congo red staining was applied. Diffuse amorphous eosinophilic substance was deposited in interlobular artery and small arteriolar artery. Combined with the abnormal free light chain (FLC) level and ratio (serum κ 340 mg/L, κ/λ 10.932), the diagnosis of systematic light-chain amyloidosis was confirmed. The patient received 3 courses of chemotherapy regimen as BCD (bortezomib 2 mg d1, 8, 15, 22, cyclophosphamide 0.3 g d1, 8, 15, 22 and dexamethasone 40 mg d1, 8, 15, 22). A hematologic partial response was achieved and serum creatinine decreased to 180 μmol/L.

Objective To investigate the clinical and pathological features of patients with a combination of Sjogren's syndrome (SS) and antineutrophil cytoplasmic antibody (ANCA) associated vasculitis with renal involvement.Methods By searching the Peking Union Medical College Hospital medical database and literature between January 1990 and June 2017,patients had a combination of SS and ANCA associated vasculitis with renal involvement were included.Data of clinical information,autoimmune antibodies,renal manifestations and renal pathology were retrieved and analyzed.Results Eighteen patients were enrolled:4 from our hospital and 14 from literature.SS was diagnosed no later than ANCA associated vasculitis in all the patients,among which 83.3％(15/18) of patients had extra-glandular and extra-renal organs involved.All the patients were tested positive for myeloperoxidase (MPO)-ANCA,and only two were protein 3 (PR3)-ANCA positive concurrently.The positivity rates of antinuclear antibody (ANA),rheumatoid factor (RF),anti-SSA antibody,and anti-SSB antibody were 83.3％(15/18),55.6％(10/18),77.8％(14/18),and 38.9％(7/18),respectively.The renal manifestations were characterized by renal insufficiency with a median serum creatinine of 174 μmol/L,hematuria,moderate proteinuria with a median 24 hour urine protein of 1.70 g,and necrotizing vasculitis with oligo-immune complex and varying degrees of interstitial damage in pathology.Conclusions A combination of Sjogren's syndrome and ANCA associated vasculitis with renal involvement is rare in clinical setting,and almost all of the patients are MPO-ANCA positive,with high probability of ANA positivity and extra-glandular involvement.Physicians should beware of ANCA associated glomerulonephritis in SS patients with inexplicable renal dysfunction and renal biopsy should be carried out in time.

Objective: To investigate the imaging features of cerebral small vessel disease(SVD) in systemic lupus erythematosus(SLE) patients with impaired renal function and their related risk factors. Methods: Seventy-six SLE patients and forty age- and sex-matched healthy controls were recruited, and SLE patients were divided into the impaired renal function group [estimated glomerular filtration rate (eGFR) <90 ml/(min·1.73 m²)] (n=38) and the normal renal function group [eGFR≥90 ml/(min·1.73 m²)] (n=38) according to their eGFR. All subjects underwent brain MRI, cognitive and psychiatric testing. The SVD scores were measured, total white matter hyperintensity (WMH) and SVD scores were calculated, and the risk factors of SVD scores were analyzed by using ordinal logistic regression. Results: SLE patients in the impaired renal function group showed higher basal ganglia PVS, centrum semiovale perivascular space (PVS), periventricular WMH, deep WMH and total SVD scores compared with normal controls or patients with normal renal function (H=44.568, 31.380, 31.172, 43.419, 24.317, P<0.001) . The ordinal logistic regression analysis showed that C-reactive protein was a risk factor for SVD in patients with SLE(OR=1.323, P<0.01). Conclusion SLE patients with impaired renal function had a higher SVD burden on MR imaging, particularly PVS in the basal ganglia and deep WMH, which was affected by the C-reactive protein level.

Objective To evaluate the predictive factors and renal outcomes of idiopathic membranous nephropathy (IMN) in patients with type 2 diabetes (T2DM).Methods In this retrospective study,clinical data of 101 IMN patients with T2DM and 96 patients with diabetic nephropathy (DN) were consecutively collected.Logistic regression was used to assess potential clinical factors indicating IMN and COX regression was employed to analyze risks of IMN in developing to endstage renal disease (ESRD),as compared with that of DN,in patients with T2DM.Results In a multivariate model,age ≥55 years old,presence of nephrotic syndrome,estimated glomerular filtration rate (eGFR) ＞ 60 ml · min-1 · (1.73 m2)-1,duration of diabetes≤5 years and absence of diabetic retinopathy,were associated with IMN,as compared with DN,in patients with T2DM.In T2DM patients presented with nephrotic syndrome,age≥55 years old,eGFR ＞ 60 ml· min1· (1.73 m2)-1,duration of diabetes≤5 years and absence of diabetic retinopathy,were also associated with IMN,as compared with DN.Receiver operating characteristic curve (ROC) showed eGFR 65.5 ml · min-1 · (1.73 m2) 1 was an optimal cutoff in differentiating DN and IMN.DN was associated with 16.8 times as high risk of incident ESRD as compared with IMN in T2DM patients.Conclusions In patients with T2DM,age≥55 years,presence of nephrotic syndrome,early stage of CKD,duration of diabetes≤5 years and absence of retinopathy,may indicate IMN rather than DN.T2DM patients with IMN have much better renal prognosis as compared with DN.

Objective To analyze the clinic-pathological data and peritubular capillary (PTC) injuries of malignant nephrosclerosis (MN) patients and their correlations with the long term renal survival.Methods This was a retrospective cohort study of 52 MN patients in Peking Union Medical College Hospital from January 2003 to March 2012.Their clinical data and renal biopsy samples were carefully studied.CD34 staining was performed to evaluate the PTC area,using Benign nephrosclerosis (BN,n=17) patients and glomerular minimal lesions (GML,n=19) patients as controls.Multivariate Cox proportional hazard model was used to identify the potential independent risk factors for long term renal survival.Results Fifty-two MN patients were enrolled.The sex ratio of male to female was 12:1 and the average age was (34.0±8.2) years.The maximum blood pressure (SBP/DBP) was (230.4 ± 25.0)/(156.4 ± 20.6) mmHg,companied with significant loss of eGFR and proteinuria.Glomerular sclerosis index,tubular atrophy and interstitial fibrosis correlated with eGFR and proteinuria (P ＜ 0.05).After aggressive treatment,BP control rate improved significantly (76.9％ vs 3.7％,P ＜0.01),Scr [(376.4±263.8) μmol/L vs (486.8±375.7) μmol/L,Wilcoxon test,P＜ 0.01] and proteinuria [(1.10±0.70) g/24 h vs (2.04± 1.26) g/24 h,P ＜ 0.01,n=21] also improved.PTC area in MN patients was significantly lower than those in BN patients and GML patients,and it correlated well with Scr (r=-0.553,P=0.001) and eGFR (r=0.476,P=0.004).The median follow-up time was 74 months,the cumulative renal survival rate at 1 year,5 year and 10 year was 90％,64％ and 23％,respectively.Kaplan-Meier analysis showed that the patients with higher PTC area had longer renal survival time [(114.8± 12.4) months vs (63.0±8.3) months, x2=5.312,P ＜ 0.05].Univariate Cox proportional hazard model found that unsatisfied BP control,eGFR ＜ 30 ml · min-1 · (1.73 m2)-1 upon discharge,lower PTC area,severer tubular-interstitial damage and anemia were associated with poor renal outcome.Multivariate Cox model showed that unsatisfied BP control (RR=3.89,95％ CI 1.75-8.65,P=0.001),eGFR ＜ 30 ml · min-1 · (1.73 m2)-1 upon discharge (RR=4.27,95％ CI 1.40-13.09,P=0.011) were independent risk factors for long-term renal survival.Conclusions The correlation between PTC area and renal functions in MN patients are much better than that of classic vascular changes.Unsatisfied BP control and eGFR ＜ 30 ml · min-1 · (1.73 m2)-1 upon discharge are independent risk factors for long-term renal survival.