Objective To investigate the clinicopathological characteristics of renal light and heavy chain amyloidosis (AHL). Methods Ten patients with renal AHL diagnosed by renal biopsy in Peking University First Hospital and Institute of Nephrology of Peking University from January 2015 to June 2020 were enrolled. Clinicopathological data of these patients was collected and reviewed. Results AHL typically affected older patients, with a male/female ratio of 7∶3. The clinical manifestations were mainly edema and heavy proteinuria. At the same time, 7/10 of patients presented with nephrotic syndrome, 7/10 presented with microscopic hematuria, and 3/10 presented with renal insufficiency. Laboratory examinations showed monoclonal immunoglobulin in blood and urine in all patients, and IgGλ was the most common one (5/10). Decreased serum complement could be seen in some patients. The ratio of serum free κ light chain and free λ light chain was abnormal in all patients who underwent serum free light chain test. None of the 10 patients met the diagnostic criteria of multiple myeloma. Except for one of the 10 patients who was diagnosed as Waldenstrom's macroglobulinemia, the rest were diagnosed as monoclonal gammopathy of renal significance (MGRS). Bone marrow of 2/6 of patients were positive for amyloid. Cardiac involvement was confirmed in only one patient. Renal biopsy demonstrated amorphous eosinophilic material, which was Congo red positive, was deposited in glomerular mesangial area (10/10), capillary vessels (8/10), renal interstitium (9/10), peritubular capillary walls (9/10) and arterioles (8/10). This material showed apple green birefringence under polarized light. Immunofluorescence showed that single heavy chain and single light chain were positive at the same time, which was consistent with the results of mass spectrometry analysis. Ultrastructural evaluation revealed randomly oriented, non-branching fibrils with a diameter of 8-12 nm. Conclusions Main clinical manifestations of AHL amyloidosis are edema and massive proteinuria, along with a high incidence of hematuria, a low portion of heart involvement and high frequency of whole molecule of monoclonal immunoglobulin (IgGλ dominant) by serum immunofixation electrophoresis. Renal pathology shows the commonly involved kidney compartments of amyloid deposits are glomerular capillary walls and peritubular capillary walls in patients with AHL amyloidosis.

Objective To report a rare case of renal injury secondary to Strongyloides stercoralis infection, and investigate common pathological subtypes, pathogenesis and differential diagnosis of Strongyloides stercoralis infection-associated renal injury combined with literature. Methods The pathological features of renal biopsy were analyzed by immunofloruscence, light microscope and electronic microscope. The pathological changes of digestive tract and pathogen morphology were observed through endoscope and digestive tract biopsy. The correlation between clinical-pathological features and pathological changes of kidney and digestive tract was analized. Results The 26-year-old male patient presented with nephrotic syndrome. The pathological changes of renal biopsy were consistent with minimal change disease with interstitial focal eosinophil infiltration. Laboratory examination showed that the patient had unexplained eosinophilia and increased IgE level. Hence the patient was treated with glucocorticoid. After 2 months of therapy, proteinuria decreased and turned to negative while the patient developed progressive headache, gastrointestinal bleeding and progressive decrease of hemoglobin. Emergency gastroscopy showed extensive congestion and erosion of the stomach and duodenum. Gastric mucosal biopsy showed a large number of slender "s" shape larvae in the mucosa. The patient also had bilateral lung infection, positive Escherichia coli in cerebrospinal fluid and purplish skin rash around the umbilicus. A serious infection of Strongyloides stercoralis was diagnosed. After antibiotics and anthelmintic treatment, gastrointestinal symptoms and headache disappeared, and no parasite was found in endoscopy. No recurrence of nephrotic syndrome was found during 2 years of follow-up. Conclusions Strongyloides stercoralis infection might first present with nephrotic syndrome with handful hints of digestive tract combined with eosinophilia and increased IgE levels. Therefore, in epidemic areas or patients with suspicious exposure history, it is necessary to exclude Strongyloides stercoralis infection before immunosuppressive therapy to avoid fatal complications.

Objective To investigate the clinico-pathological characteristics and outcomes of adult patients with thin basement membrane nephropathy (TBMN). Methods Patients with biopsy-proven TBMN in National Clinical Research Center of Kidney Diseases, Jinling Hospital during Jan 1, 2008 to Dec 31, 2017 were collected. The clinico-pathological characteristics, prognosis, the influencing factors of proteinuria and renal chronic lesions were retrospectively analyzed. Results Among 135 adult patients included, 116 cases (85.9%) were female, and 19 cases were males. The age was (40.56±10.30) years old. There were 30 cases (22.2%) with hypertension and 32 cases (23.7%) with overweight or obesity. Proteinuria was found in 41 patients (30.4%) with (0.65±0.19) g/24 h of urine protein, and microscopic hematuria was found in all 135 patients. Serum creatinine was normal in all patients. Glomerulosclerosis was observed in 102 cases (75.6%), in which 51 cases (37.8%) had glomerulosclerosis>10%. There were 79 cases (58.5%) with mild chronic tubulointerstitial lesions, and 53 patients (39.3%) with vascular hyalinosis. The proportions of proteinuria, chronic tubular interstitial lesion and renal vascular lesion in patients with overweight/obesity and/or hypertension were higher than those without complications (all P<0.05). Multivariate logistic regression results showed that overweight/obesity (OR=7.550, 95%CI 2.091-27.257, P=0.002) and hypertension (OR=4.424, 95%CI 1.091-17.935, P=0.037) were independent influencing factors for proteinuria, while proteinuria was the independent influencing factor for chronic tubular interstitial lesion (OR=3.151, 95%CI 1.046-9.491, P=0.041). Four patients were lost to follow-up, and the median follow-up time of the remaining patients was 64.0(24.0, 96.5) months. At the end of the follow-up, urine protein increased in 10 patients (7.4%) and estimated glomerular filtration rate decreased in 3 patients (2.2%). The above 13 cases were all complicated with overweight/obesity and 4 cases with hypertension. The urine test and renal function in the remaining 118 patients didn't change significantly from baseline. Conclusions The incidences of proteinuria and renal chronic lesion are high in adult TBMN patients. Overweight/obesity and hypertension may cause a poor prognosis, and TBMN patients without metabolic abnormalities probably have good prognosis, but need long-term follow-up.

Objective To determine the prevalence of sarcopenia and explore related influencing factors of sarcopenia in maintenance hemodialysis (MHD) patients. Methods MHD patients aged ≥18 years old and receiving therapies of ≥3 months from March 2019 to December 2019 in Blood Purification Centre of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were retrospectively enrolled in this study. General data of the patients were collected. Grip strength was measured by the Jamar dynamometer and the chair stand was measured by a chair of standard height to assess skeletal muscle strength and appendicular skeletal muscle mass was measured by dual energy X-ray absorptiometry. Baseline data between MHD patients with and without myasthenia were compared. Logistic regression analysis method was used to analyze the influencing factors for sarcopenia in MHD patients. Results A total of 125 MHD patients were enrolled, with 68 males (54.4%), age of (59.4±14.9) years and median dialysis age of 51.0(23.5, 101.0) months. Sarcopenia was diagnosed in 39 cases (31.2%). Compared with MHD patients without sarcopenia, age, tumor necrosis factor-α, von Willebrand factor (vWF) and proportion of using α ketones were higher, and serum carbondioxide combining power (CO₂CP), prealbumin, albumin and proportion of regular exercise were lower in MHD patients with sarcopenia (all P<0.05). Multivariable logistic regression analysis results showed that low CO₂CP (OR=0.717, 95%CI 0.576-0.892, P=0.003), high vWF (OR=1.037, 95%CI 1.016-1.058, P<0.001) and no regular exercise (OR=0.309, 95%CI 0.118-0.810, P=0.017) were independent influencing factors of sarcopenia in MHD patients. Conclusions The prevalence of sarcopenia in MHD patients is high. Low CO₂CP, high vWF and no regular exercise are independent influencing factors for sarcopenia in MHD patients.

Objective To observe heart rate circadian rhythm in patients with chronic kidney disease (CKD) stage 5 and to analyze the effects of parathyroidectomy (PTX) on heart rate circadian rhythm in severe secondary hyperparathyroidism (SHPT) patients. Methods A cross-sectional observation was performed in 213 patients with CKD stage 5 and 96 controls, and the patients were divided into those with severe SHPT (PTX group, n=70) and without severe SHPT (non-PTX group, n=143). Forty-six PTX patients were followed up prospectively. The baseline data were compared among these groups. Holter electrocardiogram was performed for each participant. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Multiple linear regression analysis was used to analyze the related factors of heart rate circadian rhythm in patients with CKD stage 5. Results The 24-hour, daytime and nighttime mean heart rate in patients with CKD stage 5 were all higher than those in controls, especially in PTX group (all P<0.05). The night/day heart rate ratios of controls and CKD stage 5 patients were (0.81±0.08) and (0.91±0.08) respectively (P<0.01). Correlation analysis showed 24-hour and daytime or nighttime mean heart rate in patients with CKD stage 5 were positively correlated with serum levels of phosphorus and ln(alkaline phosphatase), while nighttime mean heart rate and night/day heart rate ratio were positively related with serum intact parathyroid hormone level. After adjusting with postoperative follow-up period (median time: 10.9 months), 24-hour and nighttime mean heart rate, and night/day heart rate ratio in PTX patients all decreased significantly (all P<0.01). Conclusions Heart rate is increased and circadian rhythm is abnormal in patients with CKD stage 5, which are related with mineral and bone disorder. PTX significantly decreases 24-hour and nighttime mean heart rate in severe SHPT patients, and improves the heart rate circadian rhythm.

Objective To explore the regulatory role of exosomes in calcification of rat vascular smooth muscle cells（VSMC）induced by high phosphorus. Methods VSMC (A7r5 cells) were cultured in vitro and randomly divided into three groups: normal phosphorus group (0.9 mmol/L), high phosphorus group (2.6 mmol/L) and high phosphorus exosomes induction group (i.e. the exosomes extracted from high phosphorus group were added to VSMC in normal culture). Until the 7th day of culture, the culture medium of normal phosphorus group and high phosphorus group obtained during the change of cell culture medium was collected, and the precipitate was obtained by ultracentrifugation and suspended by phosphate buffered saline. The protein content of the precipitate was determined by BCA protein quantitative method. The precipitates were identified. The structure and size of exosomes were observed by transmission electron microscope. The exosomes marker proteins tumor susceptibility gene 101 protein (TSG101) and CD9 were detected by Western blotting. The miRNA in exosomes was extracted, and the expression of related miRNA (miR-30b, miR-204, miR-211) were observed by real-time quantitative PCR. After 7 days of cultivation, the exosomes uptake process of VSMC in high phosphorus exosomes induction group was observed. The calcium deposition was detected by Alizarin stain, and the calcium content was detected by O-cresol complex copper. The content of alkaline phosphatase was detected by colorimetry. The protein expression of Runx2 was quantified by Western blotting. Results (1) The precipitate obtained by ultracentrifugation of the cell culture fluid was identified as exosomes by electron microscopy morphology. Western blotting confirmed that the expression of the exosomal marker proteins TSG101 and CD9 were positive. (2) The exosomes were rich in miRNAs. The expression of miR-30b, miR-204, miR-211, which negatively regulated the transcription of Runx2, was significantly down-regulated in the high-phosphorus group compared with the normal group (P<0.05). (3) After culturing rat VSMC with high phosphorus for 7 days, calcium salt deposition was obvious. Compared with the normal phosphorus group, calcium content and alkaline phosphatase activity were significantly increased (both P<0.05), and Runx2 expression was also significantly increased (P<0.05). (4) Added the obtained high-phosphorus exosomes to the normal cultured VSMC, the exosomes could be taken up by VSMC and successfully induced VSMC calcification. The levels of cell calcification indicators and Runx2 expression were significantly increased. Conclusions High phosphorus induces calcification of VSMC and promotes the increase of Runx2 expression. The mechanism may be realized by releasing exosomes from VSMC to transmit cell signals.