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The paper reports a rare case of alkaptonuria (AKU) with IgA nephropathy, and analyzes its clinical manifestations, imaging findings, pathological features, gene diagnosis and treatment process, so as to provide reference for the diagnosis and treatment of the disease. The clinical symptoms of the patient were mainly black urine, microscopic hematuria and proteinuria. Renal pathology showed mild mesangial hyperplasia IgA nephropathy, and renal tubular epithelial cytochrome deposition. Genetic analysis indicated that a pathogenic mutation was detected on the AKU-related homogentisate 1, 2-dioxygenase gene possibly associated with the phenotype of the patient. Genetic testing and renal pathology were effective methods to make a definite diagnosis for the case.
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Rituximab is currently used as a first-line therapy for phospholipase A 2 receptor-associated membranous nephropathy due to its good efficacy and safety. Although the remission rate after rituximab treatment is more than 60%, nearly 40% patients still do not respond to treatment. We used obinutuzumab to treat 3 cases of rituximab resistant PLA 2R-associated membranous nephropathy. After the first dose of 1 000 mg with or without additional dose, the amount of anti-PLA 2R antibody and urinary protein decreased significantly and the adverse reactions were mild. The results show that obinutuzumab has a certain therapeutic effect on rituximab resistant PLA 2R-associated membranous nephropathy, but the time of follow-up observation is short and can only be used as individual cases, which needs to be confirmed by a large sample and high-quality prospective cohort study.
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Objective To investigate the relationship between the incipient serum C-reactive protein (CRP) and clinicopathologic features in anti-neutrophil cytoplasmic antibody associated vasculitis (AAV).Methods Data of 138 consecutive AAV patients were collected.According to their serum CRP levels,patients were divided into group 1 with normal CRP,group 2 with slightly increased CRP and group 3 with severely increased CRP.Clinical features of AAV and histopathologic features of the kidney injury were compared among groups.Results CRP levels increased in 77.53％ AAV patients on admission.Patients in the group of severely increased CRP had the highest levels of BVAS,serum C3,serum ANCA titer,leukocyte counts and the lowest levels of hemoglobin and albumin among the 3 groups (all P ＜ 0.05).The mortality during the stage of therapy was highest in patients with severely increased CRP (P ＜ 0.05).The focal kidney damage was more obvious in patients with severely increased CRP.There was no significant difference in renal prognosis among patients with different CRP levels.Conclusion The levels of incipient serum C-reactive protein of AAV vary in different patients and are positively correlated with patients' inflammation status as well as the disease activity,but are not correlated with the severity of kidney injury.
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Objective To evaluate the effect of 6% hydroxyethyl starch 130∕0. 4 on acute kidney injury in elderly patients in a prospective, multicenter, randomized, double?blind, controlled clinical tri?al. Methods A total of 120 patients of both sexes, aged 65-82 yr, weighing 56-83 kg, of American So?ciety of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for elective orthopaedics and hernia surgery, were divided into either hydroxyethyl starch group ( group HES) or lactated Ringer′s solution group ( group LR) , with 60 patients in each group. Hydroxyethyl starch and lactated Ringer′s solution were infused intra?venously at a rate of 7. 5 ml∕kg during 1st hour of surgery in HES and LR groups, respectively. Lactated Ringer′s solution was then infused at a rate of 5 ml∕kg starting from 2nd hour of surgery until the end of sur?gery in both groups. Before surgery, at the end of surgery and at 1, 3 and 5 days after surgery, blood sam?ples and urine specimens were collected for determination of the concentrations of neutrophil gelatinase?asso?ciated lipocalin, interleukin?18 (IL?18), plasma creatinine, urine β2 microglobulin and urine albumin. The estimated glomerular filtration rate was calculated. Results The level of urine IL?18 was significantly higher at each time point after surgery than before surgery and immediately after the end of surgery ( P0.05) . Conclusion Compared with lactated Ringer′s solution, 6% hydroxyethyl starch 130∕0.4 does not aggravate acute kidney injury in elderly patients.
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Objective To observe the expressions of oxidized low density lipoprotein ( OxLDL ) receptor CD36 in kidney tissue of diabetic rats and in tubular cells incubated with OxLDL, and to explore the association of CD36 with the tubular injury and renal fibrosis in the process of diabetic nephropathy. Methods Diabetic rat model with hyperlipidemia was established by feeding with high sugar and fat diet and injection of low dose streptozotocin intraperitoneally. The expression of CD36 in kidney tissues was analyzed immunohistochemically. Meanwhile, the tubular sclerosis and fibrosis injury index were estimated and calculated. NRK-52E cells were stimulated with 50 mg/L OxLDL for 5, 10, 24, and 48 h, or 100 and 150 mg/L OxLDLs for 2 and 3 days. The protein expression of CD36 was detected by Western blot. Results The expression of CD36 in the renal tubulointerstitium of diabetic rats was increased comparing to that in control rats, and was localized mainly at tubular region. The renal tubular damage index(STI)ofdiabetesgroupwashigherthanthatincontrolgroup(5.54±1.5vs0.65±0.15,P<0.05). OxLDL stimulated CD36 expression in NRK-52E cells in a dose-and time-dependent manner. Conclusion The expression of CD36 was increased in renal tubular of diabetic rats, in consistent with STI. OxLDL increased CD36 expression in NRK-52E cells. These results suggest that the expression of CD36 is associated with renal tubular damages in experimental rat diabetes.
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ObjectiveTo investigate the intervention effects of fluoxetine on hypothalamic-pituitary-thyroid (HPT) axis function changes in post-stroke depression (PSD) patients.MethodsMild to moderate stroke patients were enrolled and blood T3,T4,FT3,FT4 and TSH were measured at day 0,1,7,14,21 and 3 months.At day 7,thyroid hormone releasing hormone (TRH) stimulation test were performed.After evaluated with the anxiety scale screening using the HAMD scale assessment at day 21,the subjects were divided into simple stroke subgroup ( ＜8 points,25 cases) and PSD sub-group ( ≥ 8 points,18 cases),with 16 healthy age and sex matched individuals as control group.In the 2nd stage,TRH stimulation test were performed in PSD patients before and after 7 days of fluoxetine administration.ResultsCompared with control group,stroke patients presented lower FT3 (P ＜0.05 ) and higher serum TSH (P ＜ 0.05) at day 0,1,7,14.Furthermore,PSD patients presented lower FT3,TSH levels and higher FT4 levels than simple stroke patients did(P＜0.05).At day 21 and month 3,T3,T4,FT3,FT4 and TSH levels in stroke patients were not different from those in control group(P ＞ 0.05).TRH test showed that the responses in PSD patients were lower than those in simple stroke patients( (2.65 ±0.42)μIU/ml vs (5.31 ±0.68 ) μIU/ml,P ＜ 0.05 ).Correlation analysis showed HAMD scores correlated with TSH level changes and TSH0 ～30 in PSD subgroup closely( r=0.35,0.25,P＜0.01 ).In the 2nd stage,TRH test showed that PSD patients who took fluoxetine presented a lower TSH level change than PSD patients who did not( (4.61 ± 2.02) μIU/ml vs (7.05 ± 2.12) μIU/ml,P ＜ 0.05 ).ConclusionPSD patients present a long and severe HPT axis function inhibition,which may due to TRH deficiency,and fluoxetine may improve this abnormality.
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In subclinical diabetic nephropathy with glomerular hyperfiltration,the renal size parameters are increased significantly,and this change sets in as early as before the appearance of microalbuminuria.The average kidney length discriminator value for glomerular hyperfiltration by receiver operating characteristic (ROC) curve analysis is 10.53 cm,with the best sensitivity,higher specificity and total coincidence rate,and can be a clinical indicator for screening early diabetic nephropathy with glomerular hyperfiltration.
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Objective To investigate the association of radial arterial calcification damage with bone mineral density (BMD) and bone metabolism biomarkers in uremia patients.Methods Sixty-seven incident hemodialysis patients were recruited into uremic group.Serum creatinine,calcium,phosphorus,lumbar spine and femoral neck BMD were measured.Parathyroid hormone (iPTH),25OHD,1,25(OH)2D,fibroblast growth factor (FGF) 23,bone specific alkaline phosphates (BAP) and osteocalcin (BGP),type Ⅰ collagen pyridine crosslinked C-telopcptidc (ICTP) were detected.Radial artery calcification was analyzed by von Kossa staining and transmission electron microscopy.Arterial type Ⅰ collagen (Col Ⅰ) expression was examined.Twenty-three healthy cases received serum and BMD examination only as control.Results Uremic patients presented higher serum phosphate,iPTH,FGF23,lower serum calcium,25OHD,1,25 (OH)2D (all P ＜ 0.05),and lower lumbar spine and femoral neck BMD (all P ＜ 0.01) compared to controls.Significant calcium deposit was observed in radial arteries in 24 uremic cases (35.8％),including 10 cases of diabetes.Immunohistochemistric assay confirmed that Col Ⅰ expression increased around calcification site and electron microscope revealed that more calcium and phosphorus plaque attached among collagen fibers.No correlation was showed between iPTH and radial artery calcification (r =-0.08,P =0.306),but after stratified by iPTH levels,correlation of iPTH and calcification was found in low iPTH (＜ 150 ng/L) group and high iPTH group (＞ 300 ng/L) (r =-0.41,0.31,P=0.044,0.023).Diabetes,lumbar spine and femoral neck BMD,ICTP,FGF23 were correlated with arterial calcification (r =0.62,-0.25,-0.43,0.34,0.86,P =0.000,0.001,0.012,0.018,0.000).Multiple regression analysis showed femoral neck BMD,ICTP,FGF23 levels were independently associated with radial arterial calcification (β =-0.221,0.181,0.260,P =0.021,0.024,0.036).Conclusion In uremic patients,reduced BMD,abnormal bone turnover rate,especially accelerated bone reabsorption,and increased serum FGF23 level are independently associated with radial artery calcification.
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Objective To investigate the expression of inflammatory mediators in renal tubular epithelial cells in patients with diabetic nephropathy (DN) and to explore the possible clinicopathological significance. Methods Twenty-three patients with DN diagnosed by renal biopsy and 10 patients with renal cell carcinoma undergone nephrectomy were allocated into DN group and control group, respectively. The renal expression of NF-κB p50, NF-κB p65, NF-κB p65 mRNA, MCP-1, OPN, α-SMA, and FN was detected by immunohistochemical or in situ hybridization assay. Serum creatinine, urinary N-acetylglucosaminedase (NAG), urinary albumin and 24-hour urinary protein were detected. The correlation between these inflmmnatory markers and clinicopathological data were analyzed. Results (1)Among all the 23 DN patients, granular degeneration of the renal tubular epithelium, focal tubular atrophy, infiltration of inflammatory cells and interstitial fibrosis were apparent, and none of these were found in control group. (2) Immunohistochemical and in situ hybridization assay showed that, compared with control group, expression of these factors increased significantly in renal tubular cells or interstitium in DN patients, and expression of α-SMA or FN was not found in tubular epithelial cells. (3)Statistics assay showed the tubular NF-κB p65 protein expression was correlated with all of the following factors: NF-κB p50 protein (r=0.792) and NF-κB p65 mRNA (r=0.763), tubular MCP-1 (r=0.825) and OPN (r=0.869) expression, interstitial α-SMA (r=0.327) and FN (r=0.432) expression, proteinuria(r=0.710), estimated glomerular filtration rate (eGFR) (r=-0.728), and urinary NAG (r= 0.930), P<0.01 respectively. Conclusion Tubular inflammation may play a role in the pathogenesis and progression of DN.
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Objective To examine the changes of histological parameters of radial artery in uremia,and to explore their effects on arterial stiffness.Methods Sixty uremic patients underwent arteriovenous fistula surgery for hemodialysis and 20 healthy subjects received healthy examination were collected as uremia group and control group, respectively.Segments of radial arteries were obtained from all of uremic subjects and were evaluated by HE, Masson, van Kossa staining and electron microscopy.The expressions of osteopontin (OPN), α-SMA and elastin in arterial wall were detected by immunostaining, and apoptotic cells were determined by TUNEL assay.All of the subjects in the two groups received brachial ankle pulse wave velocity (baPWV) examination and the results were compared.The associations among histological parameters and baPWV were analyzed.Results More than one half (34/60) of artery samples presented uniformly thickening intima, in which most of cells expressed α-SMA and a few cells underwent apoptosis.The subendothelial matrix was abundant in collagen fibers, and no calcium deposition was found.The media thickened obviously, with increased collagen fibers, reduced elastin, unchanged α-SMA expression, and a few apoptotic smooth muscle cells.Two thirds uremic arteries expressed OPN, of which only one half had significant calcium deposition.The adventitia thickened and no calcium deposition was found.The baPWV level in uremic subjects was ( 18.5 ± 3.2 ) m/s, far greater than that in control subjects ( P ＜ 0.001 ).Statistical analysis showed that baPWV value was correlated with media thickness, calcification degree, and collagen content positively, and with elastin expression negatively.For diabetic uremic subjects, the OR values of vascular calcium deposition and remarkably-elevated baPWV value were 3.1, 2.3, respectively.Conclusions Radial arterial intima often presents hyperplasia which is not related with baPWV increment in uremia.Arterial media calcification and collagen content incremental are the most two protuberant characteristics in uremia, especially in ones accompanied with diabetes.Medical calcification, collagen accumulation, and e]astin reduction may contribute to the increased arterial stiffness in uremia.
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Objective To investigate the correlation between serum bone metabolism biomarkers and bone mineral density (BMD) in chronic kidney disease (CKD) patients with different stages. Methods Seventy-eight CKD patients were enrolled in this study and were assigned to different groups according to their ereatinine clearance (Cer). Patients with Cer ≥ 15 ml/min were divided into 4 groups based on clinical CKD 1-4 stage standard, and those with Ccr<15 ml/min were divided into two groups of hemodialysis (HD) and non-HD. Their levels of serum calcium, phosphorus, alkalinity phosphatase (ALP), urea, Ser, osteocalein (gla-protein, OC), calcitonin (CT), intact parathyroid hormone (iPTH), osteoprotegerin (OPG) and BMD were detected respectively. Results (1) The serum levels of OPG, iPTH and phosphorus increased significantly in stage 3, 4, 5, respectively (P<0.01), and serum OPG level was elevated to (5.1±1.34) ng/L after HD, which was significantly higher than (3.35±0.76) ng/L before HD (P<0.05). The levels of serum OC, CT, calcium, ALP were not significantly different among patients with different CKD stages, while the level of OC was elevated in HD patients (P<0.05). The femoral WARDS triangle BMD of CKD stage 4 patients decreased to 0.77±0.09, which was less than the value of CKD stage 1 patients (P<0.01), with litde influence from hemodialysis treatment. (2) The level of serum OPG was positively correlated with the levels of serum phosphorus, iPTH, OC (r = 0.51, 0.39, 0.36,all P<0.01), and it was negatively correlated with the level of Ccr (r =-0.70, P<0.01). The femoral WARDS triangle BMD was negatively correlated with the levels of iPTH, OC, phosphorus and OPG (r =-0.59,-0.51,-0.45,-0.48, all P<0.05). Conclusions Most of serum bone metabolism biomarkers change according to the declined level of Cer. Compared with serum phosphorus, the levels of iPTH, BGP and femoral WARDS triangle BMD, serum OPG may be early diagnosticmarkers of renal osteodystrophy in CKD patients.
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Objective To evaluate the effect of ALD on podocyte apoptosis and the possible roles of Akt in ALD-induced apoptosis. Methods The cultured rat podocytes were incubated with increasing concentrations of ALD (10-9~10-5 mol/L) for variable time periods. Apoptosis was evaluated by cell nucleus staining and flow cytometry. RT-PCR was used to examine the expression of mineralocorticoid receptor (MR)and 11 Beta-hydroxysteroid dehydrogenase type 2 (11?-HSD2) mRNA in podocyte. Activation of Akt/PKB was evaluated by performing Akt kinase assay. Results ALD induced podocyte apoptosis in a dose- and time-dependent manner. The proapoptotic effect was attenuated by the presence of spironolactone (10-7mol/L). The expression of MR and 11P-HSD2 mRNA was demonstrated in the podocytes by RT-PCR. ALD also inhibited the activity of Akt in a dose-dependent manner, but the inhibitory effect was significantly ameliorated by the presence of spironolactone. The activity of Akt was negatively correlated with podocyte apoptosis. Conclusion ALD induces apoptosis in rat podocytes through the signaling mechanism by which Akt is inhibited.
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There is an independent-regulated renin-angiotensin system(RAS)in kidney.Most of patients with hypertension or kidney diseases present increased renal RAS activity,which maintains body water and sodium balance,but contributes to the occurrence of hypertension and renal damage progression.The article reviewes some recent basic and clinical researches,focusing on the renal RAS activation mechanisms,consequences and clinical significance of the intervention of RAS blockers,which may help us recognize local RAS function of kidney,explore the treatment strategies to control hypertension and slow chronic kidney disease progression.
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Objective To investigate the effect of surfactant protein A (SP-A) on the production of MIP-2 and binding activity of NF-?B in rat tubular epithelial cells, and evaluate its possible role in renal inflammation. Methods Confluent cultures of NRK-52E cells (a renal tubular epithelial cell line of rat origin) were pretreated with various concentrations of SP-A(0 to 80 ?g/ml) and stimulated by lipopolysaccharide (LPS) (10 ?g/ml) with 2% serum. MIP-2 expression was measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). The effect of SP-A on NF-?B binding activity was assessed by electrophoretic mobility shift assay (EMSA). Results MIP-2 mRNA and protein was expressed and up-regulated in NRK-52E cells stimulated by LPS. The expression of MIP-2 was down-regulated by SP-A. NF-?B binding activity was inhibited by SP-A in a concentration-dependent manner. Conclusion SP-A binding activity and down-regulates the expression of MIP-2 in renal tubular epithelial cells, which may play an important role in the modulation of renal tissue inflammation.