Caracterización de enfermedades glomerulares: análisis de 22 años de biopsias renales / Frequency of glomerular diseases in an analysis of 550 kidney biopsies

BACKGROUND: The frequency of glomerular diseases is dynamic and varies according to geographic area. AIM: To evaluate the frequency of primary and secondary glomerulopathies, their demographic profile and main clinical characteristics. MATERIAL AND METHODS: Renal biopsies from native kidneys performed between 1999 and 2020 were retrospectively reviewed. Demographic characteristics, clinical presentation, most relevant laboratory tests, frequency of primary and secondary glomerulopathies were analyzed. RESULTS: We analyzed 550 kidney biopsies from patients with a median age of 48 years (64% females). Nephrotic syndrome was the main indication for renal biopsy. Primary and secondary glomerulopathies occurred with similar frequency. Within the primary glomerulopathies, membranous nephropathy (34.1%) was the most common, followed by IgA nephropathy (31.1%) and focal segmental glomerulosclerosis (14.1%). Among the secondary glomerulopathies, lupus nephropathy was the most common (41.7%), followed by pauciimmune glomerulonephritis (27.1%) and diabetic nephropathy (6.4%). When comparing the results with other regions, significant differences were observed with reported frequencies in United States, Europe, Asia and the rest of Latin America. CONCLUSIONS: The most common primary glomerulopathies were membranous nephropathy and IgA nephropathy. Among the secondary glomerulopathies lupus nephropathy and pauci-immune glomerulonephritis were the most common. Compared to international registries, we observed a high proportion of membranous nephropathy and pauci-immune glomerulonephritis.

Establishment of a diagnostic model for glomerular micro thrombosis in patients with lupus nephritis based on machine learning / 中华风湿病学杂志

Objective:To establish a diagnostic model for glomerular micro thrombosis (GMT) in lupus nephritis through clinical indicators.Methods:A continuous collection of patients diagnosed with lupus nephritis (LN) by renal biopsy in the Department of Nephrology, Shenzhen Second People's Hospital, from January 2010 to March 2021. All patients were admitted and discharged through the inclusion and exclusion criteria. Demographic data, clinical characteristics, biochemical indicators, and immune indicators were collected. A GMT diagnosis model was established from the most important variables among the abovementioned variables through machine learning and Logistic stepwise regression analysis. The model was presented through a nomogram. The receiver operating characteristic curve (ROC), the clinical decision curve and the calibration curve were used to evaluate the model discrimination, clinical use and accuracy, respectively. The internal verification of the model was carried out by repeated sampling 500 times by the Bootstrap method.Results:There were a total of 129 patients with lupus nephritis including the study, including 117 females (90.7%); the average age was (34±11) years. There were 39 patients with GMT (30.2%). Using machine learning to screen out the top 10 important variables from 47 candidate variables, then through logistic stepwise regression analysis, five variables were further screened to establish the diagnostic model of GMT, namely hemoglobin [ OR(95% CI)=0.966(0.943, 0.990), P=0.005], serum C3 [ OR(95% CI)=0.133(0.022, 0.819), P=0.030], systolic blood pressure [ OR(95% CI)=1.027(1.005, 1.049), P=0.017], lymphocyte count [ OR(95% CI)=0.462(0.213, 0.999), P=0.049], and TT [ OR(95% CI)=1.260(0.993, 1.597), P=0.057]. Draw up the equation of the GMT diagnosis model of lupus nephritis and establish a nomogram to present the model. The area under curve (AUC) of the diagnostic model was 0.823, 95% CI(0.753, 0.893), indicating that the model had a reasonable degree of discrimin-ation. The Hosmer-Lemeshow test showed a perfect fit between the predicted GMT risk and the observed GMT risk ( χ2= 14.62, P=0.067). The clinical decision curve and clinical impact curve reflect that the model had a good clinical application value, especially when the threshold probability is between 0.4 and 0.6, the application value is more significant. In addition, after 500 repeated samplings by the Bootstrap method, the average AUC was 0.825, 95% CI(0.753, 0.893), which is basically the same as the AUC obtained by the original model. Conclusion:We established a diagnostic model of GMT inLN based on clinical indicators through machine learning and logistic stepwise regression analysis. It is used for early diagnosis of the risk of GMT before the renal biopsy.

Ultrasound-guided percutaneous renal biopsy at a university hospital: retrospective analysis of success and complication rates / Biópsia renal percutânea guiada por ultrassonografia: análise retrospectiva de sucesso e complicações em um hospital universitário

Abstract Objective: To evaluate the success and complication rates of ultrasound-guided renal biopsy at a tertiary care hospital. Materials and Methods: This was a retrospective analysis of 97 ultrasound-guided renal biopsies, all performed by the same radiologist, between 1 March, 2017 and 31 October, 2019. Results: Of the 97 biopsies evaluated, 87 had a definitive pathological diagnosis. In five cases (5.4%), the biopsy results were inconclusive and a second procedure was required. In seven procedures (7.6%), there were complications, all of which were properly resolved. Conclusion: Ultrasound-guided renal biopsy has proven to be a safe, effective method for the diagnosis of nephropathies, with high success rates.

Resumo Objetivo: Avaliar taxas de sucesso e de complicações de biópsias renais guiadas por ultrassonografia em um hospital terciário. Materiais e Métodos: Análise retrospectiva de 97 biópsias renais realizadas entre 1º de março de 2017 e 31 de outubro de 2019, guiadas por ultrassonografia e executadas por um único médico radiologista. Resultados: Oitenta e sete biópsias apresentaram diagnóstico anatomopatológico definitivo. Cinco biópsias foram inconclusivas (5,4%) e precisaram de um segundo procedimento. Houve complicações em sete procedimentos (7,6%), todas devidamente solucionadas. Conclusão: A biópsia renal guiada por ultrassonografia demonstrou ser um método efetivo e seguro para o diagnóstico de nefropatias, com elevada taxa de sucesso em sua execução.

Morphofunctional study on the effects of passive smoking in kidneys of rats / Estudo morfofuncional sobre os efeitos do tabagismo passivo em rins de ratos

ABSTRACT Objective To analyze whether passive inhalation of cigarette smoke causes morphological, structural, and functional changes in kidneys of rats. Methods Wistar rats, aged eight weeks, weighing on average 260g, were divided into Control Group and Smoking Group. Each group was subdivided into four groups of ten animals for morphofunctional analysis, in a period of seven and 28 days. The Smoking Group was exposed to smoke of 40 cigarettes per day, at certain times and in automated equipment for cigarette burning, called smoking machine (SM-MC-01). After the exposure period, urine and blood samples were collected for the functional analyses, and the kidneys were dissected and submitted to histological procedures for morphoquantitative analyses. Results After exposure of animals of the Smoking Group, the following were observed: lower weight gain; lower water and feed intake; decreased renal weight, diameter, and volume; reduction in cortical thickness and glomerular volume density; decrease in glomerular and capsular diameter; increase in mesangial density; decreased urine volume; increased levels of glucose, serum creatinine and microalbuminuria; decreased urinary creatinine levels and creatinine clearance rate. Conclusion Passive smoking negatively influences renal morphology and glomerular filtration rate, with effects similar to those described in the literature regarding active smoking.

RESUMO Objetivo Analisar se a inalação passiva da fumaça do cigarro proporciona alterações morfológicas, estruturais e funcionais nos rins de ratos. Métodos Ratos Wistar, com oito semanas de idade, pesando, em média, 260g, foram divididos em Grupo Controle e Grupo Tabagista. Cada grupo foi subdividido em quatro grupos de dez animais para análise morfofuncional, em um período de sete e 28 dias. O Grupo Tabagista foi exposto à fumaça de 40 cigarros por dia, em horários determinados e equipamento automatizado de queima de cigarros, denominado smoking machine (SM-MC-01). Após o período de exposição, foram coletadas amostras de urina e sangue para as análises funcionais, e os rins foram dissecados e submetidos a procedimentos histológicos para análises morfoquantitativas. Resultados Após a exposição dos animais do Grupo Tabagista, observou-se menor ganho de peso; menor consumo de água e ração; menor peso, diâmetro e volume renal; redução em espessura cortical e densidade de volume glomerular; diminuição no diâmetro glomerular e capsular; aumento na densidade mesangial; volume urinário diminuído; níveis aumentados de glicose, creatinina sérica e microalbuminúria; níveis reduzidos de creatinina urinária e redução da taxa de depuração da creatinina. Conclusão O tabagismo passivo influencia negativamente na morfologia renal e na taxa de filtração glomerular, com efeitos semelhantes aos descritos na literatura em relação ao tabagismo ativo.

Assessment of long term outcomes after buccal mucosal graft urethroplasty: the impact of chronic kidney disease

ABSTRACT Objectives To compare and assess various outcomes and success of buccal mucosal graft urethroplasty (BMGU) in patients with CKD versus patients having normal renal function. Material and Methods This was a retrospective, single centre study, during period 2013 to 2017. Patients were grouped into two groups. Group 1 had patients with estimated Glomerular Filtration Rate (eGFR)>60mL/min/1.73m2 while group 2 had patients with eGFR <60mL/min/1.73m2. eGFR was calculated according to the MDRD equation. The two groups were compared with regard to various outcomes like length, location of stricture, technique of graft placement, intra-operative blood loss (haemoglobin drop), duration of hospital stay, post-operative complications and recurrence. Results A total of 223 patients were included in study with group 1 had 130 patients and group 2 had 93 patients. Mean age of patients with CKD were higher (47.49 years versus 29.13 years). The mean follow-up period was comparable between both groups (23.29 months and 22.54 months respectively). Patients with CKD had more post-operative Clavien Grade 2 or higher complications (p=0.01) and a greater recurrence rates (p<0.001) than in non-CKD patients. On multivariate analysis, age and CKD status was significant predictor of urethroplasty success (p=0.004) (OR= 14.98 (1.952-114.94, 95% CI). Conclusions CKD patients are more prone to post-operative complications in terms of wound infection, graft uptake and graft failure and higher recurrence rates following BMGU.

Comparative analysis of primary and secondary glomerulopathies in the northeast of Brazil: data from the Pernambuco Registry of Glomerulopathies - REPEG / Análise comparativa de glomerulopatias primária e secundária no nordeste do Brasil: dados do Registro Pernambucano de Glomerulopatias - REPEG

Abstract Introduction: In Brazil, glomerulopathies are the third leading cause of chronic renal disease, accounting for 11% of dialysis patients. Studies on the prevalence of this disease in Northeastern Brazil are scarce. Objective: The aim was to describe the findings of biopsies and to conduct a comparative analysis on the clinical laboratory presentation of primary glomerulopathies (PG) and secondary glomerulopathies (SG). Methods: This was a retrospective study conducted at two public teaching hospitals in the state of Pernambuco, Northeastern Brazil. Results: A total of 1151 biopsies performed between 1998 and 2016 were analyzed. The sample consisted of 670 biopsies of native kidneys, after excluding extra glomerular diseases and unsuitable material. PG were more frequent than SG (58% vs. 42%). There was a prevalence among PG of focal segmental glomerulosclerosis (43%). Membranoproliferative glomerulonephritis and collapsing glomerulopathy, accounted for 9% and 3% of the PG, respectively. For SG, the main etiologies were lupus nephritis (67%) and infections (10%). Female sex, hematuria and an elevated level of creatinine were related to a greater chance of SG, at multivariate analysis. An increase of proteinuria reduced this chance. Nephrotic syndrome was more common among the PG, while urinary abnormalities and nephritic syndrome prevailed in patients with SG. Conclusion: This is the first registry of glomerulopathies in Northeastern Brazil. It also presents a comparative analysis of the main clinical laboratory abnormalities of PG and SG, and includes the current classifications of glomerular diseases.

Resumo Introdução: No Brasil, glomerulopatias são a terceira causa de doença renal crônica terminal, responsáveis por 11% dos pacientes em diálise. Entretanto, estudos sobre a prevalência desta patologia no nordeste do Brasil são escassos. Objetivo: O objetivo foi descrever os achados das biópsias e analisar comparativamente a apresentação clínico laboratorial entre as glomerulopatias primárias (GP) e as glomerulopatias secundárias (GS). Métodos: Estudo retrospectivo, realizado em dois hospitais públicos de ensino do estado de Pernambuco, nordeste do Brasil. Resultados: Foram avaliadas 1.151 biópsias, de 1998 a 2016. A amostra foi composta por 670 biópsias de rins nativos, após exclusão de patologias extra glomerulares e materiais inadequados. GP foram mais frequentes do que GS (58% × 42%). Dentre as GP, houve predomínio de glomeruloesclerose segmentar e focal (GESF). Glomerulonefrite membranoproliferativa e glomerulopatia colapsante foram responsáveis por 9% e 3% das GP, respectivamente. Das GS, as etiologias principais foram nefrite lúpica (67%) e infecciosas (10%). Sexo feminino, hematúria e nível elevado de creatinina estiveram relacionadas a uma maior chance de GS na análise multivariada. Síndrome nefrótica foi mais comum dentre as GP, já anormalidades urinárias e síndrome nefrítica prevaleceram nos pacientes com GS. Conclusões: Este é o primeiro registro de glomerulopatias do nordeste do Brasil. Demonstrou-se também uma análise comparativa das principais alterações clínico laboratoriais das GP e GS, com classificações atualizadas das doenças glomerulares.

Glomerular loss after arteriovenous and arterial clamping for renal warm ischemia in a swine model

ABSTRACT PURPOSE: To evaluate the glomerular loss after arteriovenous or arterial warm ischemia in a swine model. METHODS: Twenty four pigs were divided into Group Sham (submitted to all surgical steps except the renal ischemia), Group AV (submitted to 30 minutes of warm ischemia by arteriovenous clamping of left kidney vessels), and Group A (submitted to 30 minutes of ischemia by arterial clamping). Right kidneys were used as controls. Weigh, volume, cortical volume, glomerular volumetric density (Vv[Glom]), volume-weighted glomerular volume (VWGV), and the total number of glomeruli were measured for each organ. RESULTS: Group AV showed a 24.5% reduction in its left kidney Vv[Glom] and a 25.4% reduction in the VWGV, when compared to the right kidney. Reductions were also observed when compared to kidneys of sham group. There was a reduction of 19.2% in the total number of glomeruli in AV kidneys. No difference was observed in any parameters analyzed on the left kidneys from group A. CONCLUSIONS: Renal warm ischemia of 30 minutes by arterial clamping did not caused significant glomerular damage, but arteriovenous clamping caused significant glomerular loss in a swine model. Clamping only the renal artery should be considered to minimize renal injury after partial nephrectomies.

Aberrant Blood Vessel Formation Connecting the Glomerular Capillary Tuft and the Interstitium Is a Characteristic Feature of Focal Segmental Glomerulosclerosis-like IgA Nephropathy

BACKGROUND: Segmental glomerulosclerosis without significant mesangial or endocapillary proliferation is rarely seen in IgA nephropathy (IgAN), which simulates idiopathic focal segmental glomerulosclerosis (FSGS). We recently recognized aberrant blood vessels running through the adhesion sites of sclerosed tufts and Bowman's capsule in IgAN cases with mild glomerular histologic change. METHODS: To characterize aberrant blood vessels in relation to segmental sclerosis, we retrospectively reviewed the clinical and histologic features of 51 cases of FSGS-like IgAN and compared them with 51 age and gender-matched idiopathic FSGS cases. RESULTS: In FSGS-like IgAN, aberrant blood vessel formation was observed in 15.7% of cases, 1.0% of the total glomeruli, and 7.3% of the segmentally sclerosed glomeruli, significantly more frequently than in the idiopathic FSGS cases (p = .009). Aberrant blood vessels occasionally accompanied mild cellular proliferation surrounding penetrating neovessels. Clinically, all FSGS-like IgAN cases had hematuria; however, nephrotic range proteinuria was significantly less frequent than idiopathic FSGS. CONCLUSIONS: Aberrant blood vessels in IgAN are related to glomerular capillary injury and may indicate abnormal repair processes in IgAN.

Expression and clinical significance of ROBO4/ARF6 signal pathway in renal glomerulus tissue of patients with diabetic kidney disease / 解放军医学杂志

Objective To investigate the expression of ROBO4/ARF6 and its correlation to glomerular endothelial cells (MGECs) permeability at each pathological stage of diabetic kidney disease (DKD). Methods Thirty patients with DKD were enrolled (patient group), and their renal tissues obtained by biopsy were divided into incipient, manifest and advanced stages (10 each) with Tervaert pathological staging, and confirmed normal renal tissues adjacent to the renal angiomyolipoma were assigned as control group. Immunohistochemistry method of MaxVision was used to detect the expression of ROBO4/ARF6 in the specimens, and then the correlation of the expression with the clinicopathological parameters (patients' HbA1c, albuminuria, serum creatinine, eGFR) were determined using statistical software SPSS 21.0. Results ROBO4 was abundantly but ARF6 rarely expressed in normal MGECs. In DKD patients, ROBO4 was mainly expressed in MGECs, while ARF6 was expressed in both MGECs and renal tubular epithelial cells. Compared with the control group, the positive intensity of ROBO4 in patient group decreased significantly (P0.05), but was positively correlated with 24h-urinary albumin (r=0.603, P<0.01) and HbA1c (r=0.582, P<0.01). Conclusion The low expression of ROBO4 and high expression of ARF6 in MGECs of DKD patients suggest that ROBO4/ARF6 signaling pathway may participate in the DKD glomerular endothelial and vascular pathological injury and urinary protein increase.

Expression and significance of Rac1 and WAVE2 in glomerulus of high-fat diet induced C57BL/6J model mice / 天津医药

Objective To explore the expression and significance of Rac1 and WAVE2 protein in glomerulus of high- fat diet induced C57BL/6J model mice. Methods Thirty-two male C57BL/6J mice (3-week old) were randomly assigned into two groups(16 in each group). The control group was fed with basic diet (10%fat) for 4 weeks. The high-fat diet group was fed with high-fat diet (60%fat) for 4 weeks. The kidney morphological changes were examined by HE and PAS staining. The expressions of Rac1 and WAVE2 protein were examined by Western blot and immunohistochemistry analysis. Results HE and PAS results showed that there were glomeruli mesangial matrix hyperplasia and exudation in high-fat diet group compared with control group. The immunohistochemistry and Western blotting results showed that expressions of Rac 1 and WAVE2 in glomerulus were both increased in high-fat diet group compared with those of control group. Conclusion Rac1 and WAVE2 protein may be involved in glomerular injuries induced by high-fat diet.

Features of ambulatory blood pressure in 808 patients with primary glomerular disease and their correlation with target organ damage / 中华肾脏病杂志

Objective To explore the features of ambulatory blood pressure in patients with primary glomerular disease and their correlation with target organ damage (TOD).Methods Patients with primary glomerular disease admitted to the Nephrology Department,the Third Affiliated Hospital of Sun Yat-sen University from May 2010 to May 2015 were enrolled.Ambulatory blood pressure monitoring (ABPM),clinical BP,ultrasonographic assessment and other clinical data were collected.Univariate and multivariate analyses were used to ascertain the relationship between ABPM results and clinical parameters.Results 808 patients were enrolled.Patients turned out to have a higher level of 24-hour systolic blood pressure (SBP),day-time SBP,and night-time SBP as their kidney function declined (r,=0.547,0.538,0.546,P ＜ 0.01).Compared with that in CKD 1-3,The percentage of dipper blood pressure pattern decreased and that of reversed dipper blood pressure pattern increased in CKD stage 4-5 (P ＜ 0.05).A higher level of 24 h SBP was independently associated with kidney function damage (OR=1.069,P ＜ 0.01),and a higher level of night-time SBP was an independent factor affecting left ventricular hypertrophy (OR=1.033,P ＜ 0.01) and reduction of diastolic function of left ventricle (OR=1.019,P ＜ 0.01) after multivariate logistic regression analyses.Conclusion With advancing CKD stage,the level of 24 h SBP,day-time SBP,and night-time SBP was higher and the percentage of reversed dipper blood pressure pattern was higher.The parameters of ABPM were closely related to renal damage and cardiovascular injuries.

Influence of propofol on endotoxin-induced expression of VEGF receptor 2 in renal glomerular endothelial cells of rats / 中华麻醉学杂志

Objective To investigate the influence of propofol on endotoxin-induced expression of vascular endothelial growth factor (VEGF) receptor 2 in renal glomerular endothelial cells of rats.Methods The primarily cultured renal glomerular endothelial cells of Sprague-Dawley rats were seeded in 24-well plates at a density of 1×106 cells/ml (200 μl/well) and divided into 6 groups (n =35 each) using a random number table:control group (group C);introlipid group (group I);propofol group (group P);lipopolysaccharide (LPS) group (group L);LPS + introlipid group (group L+I);LPS + propofol group (group L+P).In group I,10％ introlipid was added with the final concentration of 4 μg/ml.In group P,propofol was added with the final concentration of 4 μg/ml.In group L,LPS was added with the final concentration of 10 μ g/ml.In group L+I,10％ introlipid was added with the final concentration of 4 μg/ml at 30 min before LPS with the final concentration of 10 μg/ml was added.In group L+P,propofol was added with the final concentration of 4 μg/ml at 30 min before LPS with the final concentration of 10 μg/ml was added.After 6 h of incutation,the cells were collected for measurement of cell permeability and VEGF receptor 2 mRNA expression (using RT-PCR),VEGF receptor 2 protein expression (by Western blot),and for examination of the morphology of cytoskeletal protein filamentous-actin (F-actin) with confocal microscope (by immunofluorescence).Results Compared with group C,the expression of VEGF receptor 2 mRNA and protein was significantly up-regulated,and the cell permeability was increased in L,L+I and L+P groups,and no significant changes were found in the parameters mentioned above in I and P groups.Compared with group L,the expression of VEGF receptor 2 mRNA and protein was significantly down-regulated,and the cell permeability was decreased in L+P group,and no significant changes were found in L+I group.F-actin connected closely between adjacent cells and a dense peripheral F-actin band was formed in C,I and P groups,while F-actin depolymerized,the peripheral F-actin band was disrupted,and cells shrank in L and L+I groups.In group L+P,a tighter intercellular connection of F-actin was observed and cytoskeleton was found to be intact.Conclusion Propofol can inhibit endotoxin-induced increase in the permeability of renal glomerular endothelial cells through down-regulating the expression of VEGF receptor 2 in rats.

Efeito do exercício físico e suplementação de potássio sobre a pressão arterial, metabolismo glicídico e albuminúria de ratos hipertensos / Effects of physical training and potassium supplementation on blood pressure, glucose metabolism and albuminuria of spontaneously hypertensive rats

Introdução: Ainda é controverso se ocorre sinergismo entre as diferentes medidas não farmacológicas utilizadas no tratamento da hipertensão arterial. Objetivo: Avaliar o efeito do exercício físico aeróbico, da sobrecarga oral de potássio e da sua associação sobre a pressão arterial, metabolismo glicídico, excreção urinária de albumina e morfologia glomerular de ratos espontaneamente hipertensos (SHR). Métodos: SHRs foram divididos em: Grupo Controle (SHR; dieta padrão e sedentário, n = 10); Grupo Exercício (SHR + E; treinado em esteira rolante, dieta padrão, n = 10), Grupo Potássio (SHR + K; sedentário, dieta rica em potássio, n = 10) e Grupo Exercício + Potássio (SHR + E + K; exercitado, dieta rica em potássio, n = 10). Semanalmente, foi aferido o peso corporal (PC) e a pressão arterial de cauda (PAC). Ao final de 16 semanas, foi realizado o Teste de Tolerância oral a Glicose. A albuminúria foi determinada nos períodos basal, na 8ª e 16ª semana. Após o sacrifício, foi realizada a análise do índice de esclerose glomerular e a pesagem da gordura visceral. Resultados: A PAC e o PC não variaram significativamente. Houve melhora da sensibilidade à insulina no Grupo Exercício e Grupo Potássio, mas não no Grupo Exercício + Potássio. Na 16ª semana, a albuminúria de todos os grupos foi significativamente menor que o grupo SHR Controle. O índice de esclerose glomerular e o peso da gordura visceral também foram significativamente menores em todos os grupos tratados quando comparados ao controle. Conclusão: A dieta rica em potássio e o exercício físico determinaram melhora no metabolismo glicídico, na albuminúria e na morfologia glomerular, porém, a sobreposição ...

Introduction: It is still controversial whether there are synergistic effects among different non-pharmacological interventions used in the treatment of hypertension. Objetives: To evaluate the effect of aerobic exercise, oral supplementation of potassium and their combination on blood pressure, glucose metabolism, urinary albumin excretion and glomerular morphology in spontaneously hypertensive rats (SHR). Methods: SHR were divided into groups: Control Group (SHR; standard diet and sedentary, n = 10), Exercise Group (SHR + E; trained on a treadmill, standard diet, n = 10), Potassium Group (SHR + K; sedentary, potassium supplementation, n = 10) and Group Exercise + Potassium (SHR + E + K, exercise, potassium supplementation n = 10). Weekly, body weight (BW) and tail blood pressure (TAP) were measured. At the end of 16 weeks, a Oral Glucose Tolerance Test was performed. Albuminuria was determined in the baseline period, at 8th and at 16th week. After sacrifice, the analysis of glomerular sclerosis index and visceral fat weight was performed. Results: The TAP and BW did not change significantly. There was improvement in insulin sensitivity in SHR + E and SHR + K, but not in SHR + E + K. At week 16, albuminuria in all groups was significantly lower than the SHR control. The glomerular sclerosis index and visceral fat content were also significantly lower in all groups compared to control. Conclusion: An oral supplementation of potassium and exercise led to an improvement in glucose metabolism, in albuminuria and glomerular morphology, however, the overlap of the treatments did not show synergism. .

Effect of liver X receptor on the thrombomodulin expression in human glomerular endothelial cells / 中华肾脏病杂志

Objective To explore the role of liver X receptor (LXR) agonist T0901317 on thrombomodulin (TM) expression in human glomerular endothelial cells and the possible mechanisms.Methods Different concentrations of T0901317 were used to stimulate human glomerular endothelial cells for different time,then LXRα,LXRβ expression were detected by using Western blotting analysis;the roles of T0901317 on TM mRNA and TM protein expression were observed by using real-time PCR,Western blotting and immunofluorescence assay.LXRα,LXRβ gene interference segment Si-hLXRα,Si -hLXRβ were transfected into human glomerular endothelial cells with the concentration of 100 nmol/L respectively,then the roles of Si-hLXRα,Si-hLXRβ on the TM protein and TM mRNA expression were assayed by Western blotting and real time PCR.Results Human glomerular endothelial cells expressed LXRα and LXRβ.Compared to the normal cells and DMSO group,T0901317 could significantly promote TM expression in human glomerular endothelial cells (P ＜ 0.05) and showed a time -and dose-dependent manner.TM expression in Si-hLXRα transfected group was significantly lower than that in the control group (P ＜ 0.05),while TM expression in Si-hLXRβ transfected group had no significant difference compared to the control group.Conclusions Human glomerular endothelial cells express LXRα and LXRβ.LXR agonist T0901317 promotes TM expression in human glomerular endothelial cells,which may be mainly through activating LXRa.

Study on the injury mechanism of Ang-Ⅱ to mice podocyte in the high glucose environment / 中国医师杂志

Objective To cultivate mice glomerular podocyte with high glucose and high Ang-Ⅱ,observe the morphocytology of podocyte,and investigate protein kinase C (PKC) activity,the expressions of nephrin and CD2-associated protein (CD2AP),and apoptosis of podocyte with injuries cultivations.Methods The conditions immortalization mice podocyte cell lines was cultivated,after passage and differential induce,the cell lines was divided into six groups:normal group,high glucose group,high Ang-Ⅱ] group,the above two mixed group,intervened group of PKC inhibitor,and hypertonic group.After 72 hours,cell apoptosis rate was detected with flow cytometer; PKC activity was detected with enzyme linked immunosorbent assay (ELISA) in 24 hours and 48 hours ; The expressions of nephrin and CD2AP mRNA were detected by real time-polymerase chain reaction (RT-PCR).Results (1)After 24 hours,the PKC of high glucose group and high Ang-Ⅱ group were more activated than normal group [(47.09 ± 1.19) pmol/L,(42.93 ±0.71) pmol/L,P ＜0.05].The activated phenomenon was more obvious in the mixed group.Compared to 24 hours [(58.75 ±0.71) pmol/ L,P ＜ 0.01],PKC was more activated in 48 hours (P ＜ 0.05).(2) Nephrin mRNA was reduced in podocyte exposed to high glucose and high Ang-Ⅱ at least 24 hours (56.87 ± 0.74,48.54 ± 0.86,P ＜ 0.05),and was reduced more in mixed group (11.7 ± 1.54,P ＜ 0.01).(3) CD2AP mRNA was reduced in podocyte exposed to high glucose,high Ang-Ⅱ,and mixed environment at least 48 hours (56.09 ± 1.46,67.68 ±2.58,and 54.08 ±2.74,P ＜0.05).The decrease trend of nephrin and CD2AP mRNA was restrained by PKC inhibitor(90.75 ± 1.33,P ＜0.05).(4) After 48 hours and 72 hours,the apoptosis rates of high glucose group,high Ang-Ⅱ group,and mixed group were risen compared to normal group (P ＜ 0.05).The increase of apoptosis rate can be restrained by PKC inhibitor.Conclusions High glucose,and high Ang-Ⅱ can activate the podocytes PKC activity,inhibit the expression of nephrin and CD2AP mRNAs,and induce podocyte apoptosis.PKC signaling pathway plays an important role in the injury mechanism of Ang-Ⅱ and high glucose to mice podocyte.

Variantes histológicas da glomeruloesclerose segmentar e focal primária: casuística e evolução clínica / Histologic variants of primary focal segmental glomerulosclerosis: presentation and outcome

INTRODUÇÃO: O significado clínico das variantes histológicas da glomeruloesclerose segmentar e focal primária (GESF) ainda é pouco claro. Com o objetivo de determinar a frequência das variantes da GESF e sua evolução clínica em uma população hispânica, analisamos nossos casos desta glomerulopatia. MÉTODOS: Neste estudo retrospectivo, biópsias renais com diagnóstico de GESF (de 1998 a 2009) foram analisadas e classificadas acordo com os critérios da classificação de Columbia. Os dados clínico-evolutivos foram analisados e comparados entre as variantes. RESULTADOS: Do total de 291 casos, 224 (77,0%) corresponderam a variante sem especificação (NOS), 40 casos (13,7%) a forma com lesão no polo urinário (TIP), 14 casos (4,8%) a lesão perihiliar (PH), 10 casos (3,4%) ao tipo colapsante (COLL) e três casos (1,0%) a variante celular (CEL). A idade média de apresentação foi de 26 anos (intervalo de 1 a 79), sendo 74 pacientes (25,4%) com idade inferior a 15 anos. Hipertensão arterial e disfunção renal foram os achados mais frequentes nos casos de PH e COLL. A variante PH apresentou-se, frequentemente, com proteinúria não nefrótica. Notou-se menos lesões histológicas de cronicidade em casos TIP. Houve remissão clínica em 57% dos pacientes com TIP, 23,5% dos pacientes com NOS, 22,2% dos pacientes com COLL e em nenhum paciente com PH (p < 0,01). Doença renal crônica (DRC) foi menos frequente no grupo TIP comparativamente as outras variantes (p = 0,03). Não houve diferença estatística na evolução para estágio final da doença renal entre as variantes. CONCLUSÕES: A aparência histológica não parece ser um bom marcador clínico de prognóstico na GESF. A forma COLL é uma doença com muitas diferenças para as outras variantes e pior prognóstico. A variante PH ocorre principalmente de adultos, com evolução frequente para DRC. A lesão do tipo TIP parece ser menos agressiva que as outras variantes, embora sua evolução não seja benigna.

INTRODUCTION: The clinical significance of histologic variants of primary focal segmental glomerulosclerosis (FSGS) remains unclear. With the aim to determine presentation and outcome of the variants of FSGS in a hispanic population, we studied our cases of this glomerulopathy. METHODS: In this retrospective study, all renal biopsies with FSGS (1998-2009), were classified according to the Columbia's classification. We analyzed histological, clinical and follow-up data and compared among variants. RESULTS: Among 291 cases, 224 (77.0%) corresponded to NOS variant, 40 cases (13.7%) to tip variant (TIP), 14 cases (4.8%) to perihilar (PH), 10 cases (3.4%) to collapsing (COLL) and three cases (1.0%) to cellular variant (CELL). Median age: 26 years (range 1 to 79); 74 patients (25.4%) were < 15 years of age. Hypertension and renal dysfunction were more frequent in PH and COLL cases. PH presented frequently as nonnephrotic proteinuria. There were fewer histologic chronic lesions in TIP cases. There was remission in 23.5% of patients with NOS, 57.7% of patients with TIP, 22.2% of patients with COLL and 0 patients with PH (p < 0.01). Chronic kidney disease (CKD) was less frequent in TIP than in the other variants (p = 0.03). There were not statistical differences for end-stage renal disease among variants. CONCLUSIONS: Glomerular histological appearance is not a good indicator of outcome. COLL is a disease with many differences to the other variants and bad prognosis; PH is a variant mainly of adults, with frequent evolution to CKD. TIP appears as a less aggressive, although not benign, variant.

Analysis of ultrastructural glomerular basement membrane lesions and podocytes associated with proteinuria and sclerosis in Osborne-Mendel rats with progressive glomerulonephropathy

The renal glomeruli of 12 male Osborne-Mendel (OM) rats 3 to 24 weeks old were examined by electron microscopy. Effacement of podocyte foot processes (FPs) developed at 3 weeks of age and became progressively worse over time. Loss or dislocation of the slit membrane was also found. Vacuoles and osmiophilic lysosomes appeared in the podocytes starting at 6 weeks of age. Podocyte detachment from the glomerular basement membrane (GBM) was apparent at 18 weeks of age. Laminated GBM was occasionally observed in all animals. These features might lead to the development of spontaneous proteinuria and glomerulosclerosis in OM rats.

Rhein and archen induce the apoptosis of mesangial cells in high glucose rats / 中国组织工程研究

BACKGROUND:Our previous study has already manifested that Chinese medicine Xiaokening can effectively prevent and treat the early diabetic nephropathy. OBJECTIVE:To compare the effect of rhein and archen on the apoptosis of mesangial cells of rats cultured with high glucose. METHODS:Mesangial cells were stimulated by different concentrations of rhein and archen (20, 40 and 80 μmol/L). Morphology of apoptotic cells was observed by hematoxylin-eosin staining. Karyon apoptosis was examined by fluorescence staining of DAPI. cellapoptosis rate was detected by flow cytometry. RESULTS AND CONCLUSION:The outcome of hematoxylin-eosin staining and DAPI staining indicated that the effect of rhein was much stronger than that of archen on the apoptosis of mesangial cells in the rats cultured with high glucose. Comparison of the apoptosis rate also indicated that the rhein had a stronger effect on the earlier and the later stage apoptotic rate of mesangial cells than archen. Both rhein and archen with different concentrations can induce apoptosis of mesangial cells, but the effect of rhein is much stronger.

Glomerular filtration rate is altered in children with sickle cell disease: a comparison between Hb SS and Hb SC

BACKGROUND Renal failure is common among older patients with sickle cell disease; this is preceded by subclinical glomerular hyperfiltration. Data about renal function of adults with sickle cell disease have been reported, but data on children is scarce, especially when comparing heterozygotic and homozygotic patients. OBJECTIVE The goal of this study was to investigate the glomerular filtration rate of heterozygotic and homozygotic children with sickle cell disease. METHODS The glomerular filtration rate of 11 children with sickle cell disease [7 homozygotic (SS) and 4 heterozygotic (SC)] with a mean age of 11 years (standard deviation: ± 5 years) was evaluated using standard laboratory techniques. Results are presented as descriptive analysis. RESULTS Our results suggest that glomerular hyperfiltration is present in children with sickle cell disease; this is more evident in homozygotic than heterozygotic children. CONCLUSION There is evidence of a need to monitor the renal function of children with sickle cell disease when special attention should be paid to homozygotic patients.

Effects of prostaglandin E1 on renal cell apoptosis in rats with diabetic nephropathy / 中华老年医学杂志

Objective To investigate the effects of prostaglandin E1 (PGE1) on renal cell apoptosis in rats with diabetic nephropathy(DN). Methods Totally 55 male Wistar rats were intraperitoneally injected with streptozotocin (STZ) to develop DN model.46 successfully established DN rat models were randomly divided into 4 groups:PGE1 group received PGE1 intravenously at dose of 10 μg · kg-1 · d-1 for 10 d (n=12),angiotensin converting enzyme inhibitors(ACEI) group given ACEI orally at dose of 10 mg kg-1·d-1 for 8 W(n=12),PGE1+ACEI group given both PGE1 and ACEI (n=11),DN control group(n=11) and normal control group(n=10) given saline only.All rats were killed after 8 weeks and blood samples or kidney tissue were collected.Blood urea nitrogen (BUN),serum creatine(Scr),albuminuria of 24 h were detected.Renal pathological morphology and apoptosis of renal cells were observed by HE staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) test. Results At 8 week after treatment,the 24-hour urinary albumin levels were decreased significantly in the following order:DN control group＞ PGE1 group ＞ ACEI group ＞PGE1+ ACEI group＞ control group[(374.6±54.1)μg,(570.0±72.5)μg,(253.1±28.9)μg vs.(1123.4±106.2)μg,P＜0.01 or P＜0.05].BUN[(9.3±2.6)mmol/L,(11.0±3.5)mmol/L,(8.4±2.2)mmol/Lvs.(15.1±4.0)mmol/L]and Scr [(74.5±19.2) umol/L,(83.5± 15.8)μmol/L,(64.6±17.3) μmol/L vs.(117.7±33.0)μmol/L]levels after treatment were also reduced in PGE1,ACEI and PGE1 + ACEI groups as compared with DN control group (P＜0.01or P＜ 0.05). Pathological manifestations of all treatment groups showed better results than DN group,and PGE1 + ACEI group was the best.There was no obvious apoptosis in glomerular area with on significant differences between groups.While apoptosis of renal tubules was observed in DN rats. Conclusions Renal tubule but not glomerular cell apoptosis may play some role in Prostaglandin E1 reduciug albuminuria.