Analysis on clinicopathology and prognosis of primary IgA nephropathy in children with massive proteinuria / 中华肾脏病杂志

Objective:To investigate the clinicopathological features and the prognosis of IgA nephropathy (IgAN) in children with massive proteinuria.Methods:It was a retrospective cohort study. Clinical data of IgAN children with massive proteinuria admitted to the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2008 to December 2021 were retrospectively analyzed. Patients were divided into effective group and ineffective group according to whether urine protein turned negative after 6 months of initial treatment. The follow-up endpoint event was defined as a reduction in proteinuria of less than 50% or end-stage renal disease (ESRD) achievement. MedCalc software was used to perform Kaplan-Meier survival analysis, and Log-rank test was used to compare the difference of renal survival between the two groups.Results:A total of 127 patients were diagnosed as primary IgAN by renal biopsy, of whom 57 patients with IgAN showed massive proteinuria. These 57 IgAN patients with macroproteinuria accounted for 44.9% of the total IgAN patients and were enrolled in the study. Among the 57 cases, 33 cases (57.9%) were Lee's grade Ⅲ, 11 cases (19.3%) were below Lee's grade Ⅲ, and 13 cases (22.8%) were above Lee's grade Ⅲ. The follow-up time was 4.0 (3.0,5.8) years. In the initial treatment, among 57 patients, 46 (80.7%) were effective (effective group) and 11 (19.3%) were ineffective (ineffective group). Compared with the effective group, the ineffective group had a higher proportion of concurrent AKI at the onset of disease and longer recovery time of renal function, with significant difference (7/11 vs. 13/46, χ2=4.878, P=0.027). Compared with the effective group, the proportion of Lee grade Ⅲ or above was higher in the ineffective group, and the difference was statistically significant (5/11 vs. 8/46, χ2=3.971, P=0.046). There were significant differences in endocapillary hypercellularity (E1), segmental glomerulosclerosis or adhesion (S1) and cellular/fibrocellular crescents (C2) of Oxford classification between IgAN children with Lee grade Ⅲ or below and those over Lee grade Ⅲ (11/13 vs. 20/44, χ2=6.204, P=0.013; 12/13 vs. 17/44, χ2=11.566, P=0.001; 9/13 vs. 7/44, χ2=14.131, P=0.001). Among 57 patients, endpoint events occurred in 2 patients who both were urinary protein unmitigated, and none of the children progressed to ESRD. There was no significant difference in cumulative renal survival between the two groups by Kaplan-Meier survival analysis and Log-rank test ( χ2=0.537, P=0.460) after addition of calcineurin inhibitors (CNIs) to the initial treatment ineffective group. Conclusions:Macroproteinuria is the prominent manifestation of IgAN in children. The pathological type is mainly Lee grade Ⅲ. Children with macroproteinuria have a good prognosis in the short and medium term after active treatment. For IgAN with macroproteinuria that does not respond well to initial treatment, AKI is more common at onset, and renal function recovery time is longer. The application of CNIs may have a certain effect on improving the renal outcome of IgAN with massive proteinuria.

A Case of Dent Disease in Children Presenting with Massive Proteinuria / 罕见病研究

This article reported the diagnosis and treatment of a boy with Dent disease presenting with massive proteinuria.He was 3 years old and found to have massive proteinuria during routine physical examination without hypoalbuminemia, urine protein electrophoresis indicated mainly low molecular weight proteins, with hypercalciuria, and metabolic acidosis, no diabetes, no amino acid urine, and renal ultrasound showed no renal calcium deposition, He had no mental and physical developmental delay and no abnormal family history. Gene detection revealed one missense mutation in exon 15 of the OCRL1 gene, c.1477C > T (p.Arg493Trp). After the diagnosis was confirmed, restrictions in dietary intake of calcium, sodium, and oxalate was restricted and oral potassium citrate and hydrochlorothiazide was prescribed. During two months of follow-up, we observed a decrease in urinary calcium levels and normal renal function. This article aims to improve the understanding of this disease among physicians and provide reference for the diagnosis and treatment of this disease through typical case report and review of previous literatures.

A Case of Childhood-Onset Bartter Syndrome Type 1 with Renal Dysfunction / 罕见病研究

Bartter syndrome (BS, OMIM #601678) is a rare inherited salt-losing tubulopathy characterized by hypokalemia metabolic alkalosis with secondary renin-angiotensin-aldosterone system activation. As reported, BS type 1 is generally presented prenatal and neonatal period, and symptoms usually appear before and after birth or in infancy, accompanied by severe salt loss, whilst kidney function remains mostly normal. In this study, we report a case of BS type 1 with childhood onset and proteinuria and renal impairment. The child was born preterm due to hyperamniotic fluid, but there were no apparent symptoms after birth until the age of 3 when the child began to present with polydipsia, polyuria and increased nocturnal uria. At the age of 5, she had elevated serum creatinine level and proteinuria. After admission, she was diagnosed with chronic tubulointerstitial disease and stage 2 chronic kidney disease(CKD). According to the chloride clearance test, the abnormal function of medullary thick ascending limb Henle′s loop, was confirmed and BS type 1 was diagnosed by gene sequencing. After active management of complications, kidney function of the child improved. In the long-term follow-up, the urinary protein amount of the child still increased, eGFR slowly decreased, and the child was currently in the CKD2 stage. Children with prenatal BS may not present typical clinical manifestations immediately after birth until the onset of relevant clinical symptoms in childhood. BS type 1 patients may have renal impairment, which needs to be identified in time. Clinical differentiation diagnosis between BS and Gitelman syndrome can be made by chloride clearance tests. Early diagnosis and treatment are critical to improve prognosis.

A Case of Dent Disease in Children Presenting with Massive Proteinuria / 罕见病研究

This article reported the diagnosis and treatment of a boy with Dent disease presenting with massive proteinuria.He was 3 years old and found to have massive proteinuria during routine physical examination without hypoalbuminemia, urine protein electrophoresis indicated mainly low molecular weight proteins, with hypercalciuria, and metabolic acidosis, no diabetes, no amino acid urine, and renal ultrasound showed no renal calcium deposition, He had no mental and physical developmental delay and no abnormal family history. Gene detection revealed one missense mutation in exon 15 of the OCRL1 gene, c.1477C > T (p.Arg493Trp). After the diagnosis was confirmed, restrictions in dietary intake of calcium, sodium, and oxalate was restricted and oral potassium citrate and hydrochlorothiazide was prescribed. During two months of follow-up, we observed a decrease in urinary calcium levels and normal renal function. This article aims to improve the understanding of this disease among physicians and provide reference for the diagnosis and treatment of this disease through typical case report and review of previous literatures.

A Case of Childhood-Onset Bartter Syndrome Type 1 with Renal Dysfunction / 罕见病研究

Bartter syndrome (BS, OMIM #601678) is a rare inherited salt-losing tubulopathy characterized by hypokalemia metabolic alkalosis with secondary renin-angiotensin-aldosterone system activation. As reported, BS type 1 is generally presented prenatal and neonatal period, and symptoms usually appear before and after birth or in infancy, accompanied by severe salt loss, whilst kidney function remains mostly normal. In this study, we report a case of BS type 1 with childhood onset and proteinuria and renal impairment. The child was born preterm due to hyperamniotic fluid, but there were no apparent symptoms after birth until the age of 3 when the child began to present with polydipsia, polyuria and increased nocturnal uria. At the age of 5, she had elevated serum creatinine level and proteinuria. After admission, she was diagnosed with chronic tubulointerstitial disease and stage 2 chronic kidney disease(CKD). According to the chloride clearance test, the abnormal function of medullary thick ascending limb Henle′s loop, was confirmed and BS type 1 was diagnosed by gene sequencing. After active management of complications, kidney function of the child improved. In the long-term follow-up, the urinary protein amount of the child still increased, eGFR slowly decreased, and the child was currently in the CKD2 stage. Children with prenatal BS may not present typical clinical manifestations immediately after birth until the onset of relevant clinical symptoms in childhood. BS type 1 patients may have renal impairment, which needs to be identified in time. Clinical differentiation diagnosis between BS and Gitelman syndrome can be made by chloride clearance tests. Early diagnosis and treatment are critical to improve prognosis.

Clinical characteristics and risk factors of acute focal bacterial nephritis in children / 中华肾脏病杂志

Objective:To summarize and analyze the clinical features and risk factors of acute focal bacterial nephritis (AFBN) in children.Methods:It was a retrospective cohort study. The clinical data of patients diagnosed with upper urinary tract infection in Children's Hospital Affiliated to Capital Institute of Pediatrics from July 1, 2016 to July 31, 2021 were collected, and the patients all received abdominal enhanced CT examination. According to the imaging examination results, the patients were divided into AFBN group and acute pyelonephritis (APN) group, and the clinical manifestations, laboratory and imaging examination between the two groups were compared. Logistic regression model and receiver operating characteristic curve were used to analyze the risk factors of AFBN.Results:A total of 135 patients with upper urinary tract infection were enrolled in this study, with age of 2.5 (0.5, 3.7) years old, and 68 males (50.4%). There were 67 patients (49.6%) in AFBN group and 68 patients (50.4%) in APN group. There were statistically significant differences in the highest fever temperature, duration of fever after treatment, proportion of lower urinary tract irritation symptoms, proportion of urinary tract malformation or abnormality, white blood cell count, neutrophil count, procalcitonin, C-reactive protein, proportion of pyuria, urinary β2 microglobulin and proportion of using carbapenem antibiotics between the two groups (all P<0.05). Multivariate logistic regression analysis result showed that urinary tract malformation/abnormality ( OR=3.34, 95% CI 1.23-9.10) and leukocytosis ( OR=1.25, 95% CI 1.03-1.51) were the independent risk factors of AFBN. Conclusions:The children with urinary tract infection who have high peak fever, long duration, obvious increase of inflammatory indexes and urinary β2 microglobulin may suggest AFBN. Urinary tract malformation/abnormality and high white blood cells are risk factors of AFBN.

Diagnosis and treatment of nephrotic syndrome combined with serious infection in children / 中国小儿急救医学

Infection is the most common complication of nephrotic syndrome in children.Serious infection leads to poor prognosis, and always deteriorates rapidly, especially in the infection of pneumocystis jeroveci and varicella.For the long-term use of steroid and immunosuppressor, patients with infection always have atypical clinical symptoms and the correct diagnosis is liable to be delayed.Therefore, it′s important to be well aware of medical histories, physical signs and associated laboratory tests.Timely control of infection and protection of renal function are the main principles of treatment in the children with nephrotic syndrome and serious infection.Meanwhile, daily health management should be strengthened for the patients to prevent the occurrence of infection.

Clinical analysis of ambulatory blood pressure monitoring in 170 children with kidney diseases / 中华实用儿科临床杂志

Objective:To investigate the features and advantages of ambulatory blood pressure monitoring (ABPM) applied in children with kidney diseases as well as the correlation between ambulatory blood pressure and clinical indicators.Methods:The clinical data of children with kidney diseases who were hospitalized and received ABPM in Children′s Hospital Affiliated to Capital Institute of Pediatrics from March 2012 to March 2018 were collected.Clinical blood pressure and ABPM indicators were analyzed and compared between different clinical groups.Results:(1) Among 170 cases enrolled, 69 cases (40.6%) were hypertension by measuring clinical blood pressure, 54 cases (31.8%) were ambulatory hypertension, 43 cases (25.3%) of whom had severe ambulatory hypertension, 17 cases (10.0%) had white coat hypertension, 41 cases (24.1%) were defined as masked hypertension, and 139 cases (81.8%) had impaired circadian rhythm of blood pressure.(2) Ninety-five point nine percent (163/170 cases) were detected of abnormal blood pressure by ABPM, and the rate was significantly higher than that detected by clinical blood pressure (40.6%, 69/170 cases) ( χ2=149.176, P<0.001). In the 40 cases who were administrated with antihypertensive drugs, 95.0%(38 cases) were detected to have anomalous blood pressure by ABPM, significantly more than that detected by clinical blood pressure(42.5%, 17/40 cases)( χ2=10.208, P=0.001). (3) Logistic regression analysis indicated that a prolonged clinical course of more than 3 months, obesity and nephrotic-range proteinuria were the risk factors of ambulatory hypertension, and the odd ratios were 5.345, 3.530 and 6.560, respectively.Circadian rhythm disorders of blood pressure were more common in the children with abnormal renal function than in those with normal renal function[89.7%(52/58 cases) vs.75.9%(85/112 cases)], and the difference was statistically significant ( χ2=4.626, P=0.031). Conclusions:Children with kidney diseases have a high incidence of hypertension.ABPM plays a key role in detecting hypertension and recognizing white coat hypertension.Nephrotic-range proteinuria and obesity are risk factors for ambulance hypertension, and abnormal renal function is associated with nocturnal blood pressure disorders.

Changes of pathogens in children with urinary tract infection in a single center in Beijing / 中华实用儿科临床杂志

Objective:To investigate the changes of distribution and antimicrobial resistance of pathogens in children with urinary tract infection in a single center in Beijing, and to provide references for the rational use of antibio-tics agent in clinical practice.Methods:The clinical data as well as urine culture and drug sensitivity results of children with urinary tract infection treated in the Department of Nephrology, Children′s Hospital Affiliated to Capital Institute of Pediatrics from January 2013 to May 2018 were retrospectively analyzed.According to the time of onset, the patients were divided into 2 groups, namely the 2013 to 2015 group and the 2016 to 2018 group.SPSS 17.0 software was used for statistical analysis of clinical data.Results:Among the 744 pathogenic bacteria isolated, the most common type was Gram-negative bacteria (59.4%, 442/744 strains), and the proportion of Escherichia coli ( E.coli) was the highest (39.4%, 293/744 strains). Gram-positive bacteria were the second most common (36.8%, 274/744 strains), among which, Enterococcus faecium (21.8%, 162/744 strains) accounted for the largest proportion (3.8%, 28/744 strains). Fungi were the least common type of pathogenic bacteria (3.8%, 28/744 strains). In Gram-negative bacteria, E.coli was highly resistant to Ampicillin (87.6%, 255/291 strains), but less resistant to Piperacillin/Tazobactam (12.7%, 37/291 strains). By comparing the overall distribution of Gram-positive, Gram-negative and common pathogenic bacteria in 2013 to 2015 and 2016 to 2018, the infection rate of Gram-negative bacteria (63.8%, 55.5%)was always higher than that of Gram-positive bacteria(33.1%, 40.2%), but the infection rate of Gram-positive bacteria has shown an upward trend in recent years, and the differences were statistically significant ( χ2=4.080, P<0.05). Conclusions:The main pathogenic bacteria of urinary tract infection in children are Gram-negative bacteria, and E.coli is the most common causative bacteria.However, the infection rate of Gram-positive bacteria has been increasing in recent years. E.coli is highly sensitive to Piperacillin and Tazobactam, which can be used as the adequate selection for treating urinary tract infection in children. E.coli is highly resistant to the first and the second-generation cephalosporin antibiotics, but sensitive to the third-generation cephalosporin antibiotics, such as Cefotetan.

The relationship between adherens junction and tight junction and clinical symptoms in patients with diarrhea predominant irritable bowel syndrome / 中华内科杂志

Objective:To investigate the association between adherens junction proteins E-cadherin and β-catenin and tight junction protein claudin-2 and clinical symptoms in patients with diarrhea predominant irritable bowel syndrome (IBS-D).Methods:Cecal biopsy tissues were collected from IBS-D patients ( n=26) according to Rome Ⅲ criterion and healthy controls ( n=26). The duration of symptoms, abdominal pain score and mean weekly bowel movements were recorded. Colorectal dilatation combined with restraint stress were applied to establish visceral hypersensitivity rat model. Abdominal contraction reflex (AWR) was applied to assess the visceral sensitivity in rats. The stool frequency within 1 hour was recorded after establishing the rat model. The expression of E-cadherin、β-catenin and claudin-2 were assessed by Western blot and immunofluorescence microscopy. Intercellular ultrastructure was observed by transmission electron microscopy. Results:Compared with the healthy controls, the protein expression of E-cadherin and β-catenin in cecal epithelium in IBS-D patients were significantly lower ( P=0.015 and P=0.005, respectively), while claudin-2 was significantly higher ( P=0.000). Reduced E-cadherin and β-catenin expression was associated high abdominal pain score ( r=-0.463, P=0.017 and r=-0.407, P=0.039). The lower expression of β-catenin was associated with longer duration of symptoms ( r=-0.458, P=0.019). The protein expression of E-cadherin and ?-catenin in the cecal epithelium of the visceral hypersensitivity rats were significantly lower ( P=0.004 and P=0.003, respectively), while claudin-2 was significantly higher ( P=0.008). Reduced E-cadherin and ?-catenin expression was associated high visceral sensitivity in IBS-D rats ( r=-0.639, P=0.047 and r=-0.888, P=0.001). Conclusions:Intercellular ultrastructure alterations well as cecal β-catenin and E-cadherin protein expression decrease and are associated with high abdominal pain score in IBS-D patients and hypersensitivity rats. β-catenin is further associated with prolonged duration of symptoms in IBS-D patients. The expression of E-cadherin and β-catenin may play a vital role in visceral sensitivity and intestinal barrier dysfunction in IBS-D.

Related factors analysis of poor prognosis in children with Henoch-Sch?nlein purpura nephritis / 中华肾脏病杂志

Objective:To explore the related factors of poor prognostis in children with Henoch-Sch?nlein purpura nephritis (HSPN), and provide reference for predicting and improving the prognosis of children with HSPN.Methods:The clinical and pathological data of children with HSPN hospitalized in the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics from May 2007 to June 2019 were retrospectively reviewed. According to the prognosis, the patients were divided into complete remission group and persistent abnormal group.Results:(1) Among 108 cases, there were 73 males and 35 females, with the onset age ranging from 5 to 16 years and average age of (9.5±2.8) years. The interval time from the first clinic in our hospital to the last follow-up was 2-131 months, with average of 24.8 months. Renal involvement occurred in the course of Henoch-Sch?nlein purpura from 1 day to 51 months, and the renal biopsy time was 5 days to 60 months after renal involvement. (2) Hematuria with proteinuria type and nephrotic syndrome type were predominant, and there was no significant difference between the two groups. The proportion of gross hematuria in the persistent abnormal group were significantly higher than that in the complete remission group (52.6% vs 31.4%, χ2=4.659, P=0.031). There were significant differences in serum creatinine and urea between the two groups (both P<0.05). The proportion of hyperuricemia in the persistent abnormal group was higher than that in the complete remission group (39.5% vs 21.4%, χ2=3.998, P=0.046). After clinical treatment, though there was no significant difference in proteinuria between the two groups at the beginning of the disease, the negative transformation rate of proteinuria in the complete remission group was higher than that in the persistent abnormal group after 3 months (55.7% vs 34.2%, χ2=4.562, P=0.033). (3) According to International study of Kidney Disease in Children (ISKDC) pathology classification, 14 cases (36.8%), 21 cases (55.3%), 3 cases (7.9%) withⅡ, Ⅲ, Ⅳ level in the persistent abnormal group and 21 cases (30.0%), 49 cases (70.0%), 0 case with Ⅱ, Ⅲ, Ⅳ level (70.0%) in the complete remission group after (20.16±24.86) months of follow-up, and the difference between the two groups was not statisticcally significant ( Z=-0.135, P=0.892). According to the Oxford Classification of IgA nephropathy, 36(33.3%) children had tubule-interstitial lesions (T1, 26%-50% tubular atrophy or interstitial fibrosis), and the proportion in the persistent abnormal group was significantly higher than that in the complete remission group (50.0% vs 24.3%, Z=-2.695, P=0.007). (4) Compared with T0 (0-25% tubular atrophy or interstitial fibrosis), the incidence of gross hematuria and hyperuricemia in the T1 tubule-interstitial lesion were both higher than that (respectively 63.9% vs 27.8%, χ2=13.061, P<0.001; 38.9% vs 22.2%, χ2=3.983, P=0.046). (5) Multivariate logistic regression analysis showed that renal tubule-interstitial lesion was a risk factor for poor prognosis of HSPN ( OR=2.580, 95% CI 1.055-6.310, P=0.038). Conclusions:Renal tubule-interstitial lesion is a risk factor for the persistent abnormal of HSPN. Gross hematuria and hyperuricemia are related to tubule-interstitial lesions.

The relationship between adherens junction and tight junction and clinical symptoms in patients with diarrhea predominant irritable bowel syndrome / 中华内科杂志

Objective@#To investigate the association between adherens junction proteins E-cadherin and β-catenin and tight junction protein claudin-2 and clinical symptoms in patients with diarrhea predominant irritable bowel syndrome (IBS-D).@*Methods@#Cecal biopsy tissues were collected from IBS-D patients (n=26) according to Rome Ⅲ criterion and healthy controls (n=26). The duration of symptoms, abdominal pain score and mean weekly bowel movements were recorded. Colorectal dilatation combined with restraint stress were applied to establish visceral hypersensitivity rat model. Abdominal contraction reflex (AWR) was applied to assess the visceral sensitivity in rats. The stool frequency within 1 hour was recorded after establishing the rat model. The expression of E-cadherin、β-catenin and claudin-2 were assessed by Western blot and immunofluorescence microscopy. Intercellular ultrastructure was observed by transmission electron microscopy.@*Results@#Compared with the healthy controls, the protein expression of E-cadherin and β-catenin in cecal epithelium in IBS-D patients were significantly lower (P=0.015 and P=0.005, respectively), while claudin-2 was significantly higher (P=0.000). Reduced E-cadherin and β-catenin expression was associated high abdominal pain score (r=-0.463, P=0.017 and r=-0.407, P=0.039). The lower expression of β-catenin was associated with longer duration of symptoms (r=-0.458, P=0.019). The protein expression of E-cadherin and ß-catenin in the cecal epithelium of the visceral hypersensitivity rats were significantly lower (P=0.004 and P=0.003, respectively), while claudin-2 was significantly higher (P=0.008). Reduced E-cadherin and ß-catenin expression was associated high visceral sensitivity in IBS-D rats (r=-0.639, P=0.047 and r=-0.888, P=0.001).@*Conclusions@#Intercellular ultrastructure alterations well as cecal β-catenin and E-cadherin protein expression decrease and are associated with high abdominal pain score in IBS-D patients and hypersensitivity rats. β-catenin is further associated with prolonged duration of symptoms in IBS-D patients. The expression of E-cadherin and β-catenin may play a vital role in visceral sensitivity and intestinal barrier dysfunction in IBS-D.

Clinical manifestations and pathological characteristics of Hen(o)ch-Sch(o)nlein purpura nephritis combined with hyperuricemia in children / 中华实用儿科临床杂志

Objective To analyze the relationship of clinical manifestations and pathological characteristics of Henoch-Sch(o)nlein purpura nephritis combined with hyperuricemia in children.Methods A retrospective study was conducted in 50 children with Henoch-Sch(o)nlein purpura nephritis who hospitalized at Department of Nephrology,Affiliated Children's Hospital,Capital Institute of Pediatrics from January 2014 to May 2018.The differences between the hyperuricemia group(19 cases)and the normal uric acid group (31 cases),were compared in age,sex,blood pressure,serum albumin,24-hour urinary protein,serum creatinine,triglyceride,cholesterol,high density lipoprotein,low density lipoprotein,serum uric acid,estimated glomerular filtration rate,and renal pathological characteristics,and the short-term prognosis was analyzed.Results (1) The average urinary protein in the hyperuricemia group and the normal uric acid group was (91.67 ±90.37) mg/(kg · d) and (64.62 ±43.28) mg/(kg · d),respectively and the difference was statistically significant between the both groups(t =2.04,P =0.047);and the morbidity with massive proteinuria in hyperuricemia group and normal uric acid group was 18/19 cases (94.7％)and 17/31 cases (54.8％),respectively and the difference was statistically significant between the both groups (x2 =8.930,P =0.003).(2)In all cases,there were 4 cases of glomerular pathological grade Ⅱ,43 cases of grade Ⅲ and 3 cases of grade Ⅳ.The pathological grading of hyperuricemia group and normal uric acid group was mainly grade Ⅲ,including 16/19 cases (84.2％) in hyperuricemia group and 27/31 cases (87.1％) in normal uric acid group,4 cases of grade Ⅱ in normal uric acid group and 3 cases of grade Ⅳ in hyperuricemia group,the pathological grade of hyperuricemia group was relatively severe (x2 =7.358,P =0.025).There was no significant difference about the degree of global sclerosis and mesangial proliferation between hyperuricemia group and normal uric acid group(x2 =2.426,P =0.119,x2 =0.043,P =0.836,respectively);7/19 cases (36.8％) had severe foot process lesions in hyperuricemia group,which was significantly higher than that in normal uric acid group [4/31 cases(12.9％)] (x2 =3.934,P =0.047).In hyperuricemia group,tubulointerstitial lesions were found in 9/19 cases (47.4％) of (+) grade and 10/19 cases (52.6％) of (+ +) grade,and 12/31 cases (38.7％) had normal tubulointerstitium in normal uric acid group,(+) and (+ +) grade lesions were also less than those in the hyperuricemia group (x2 =10.694,P =0.005).The mean scores of tubular atrophy and interstitial fibrosis were significantly higher in hyperuricemia group than that in normal uric acid group(t =2.36,P =0.001).(3) The interval from renal biopsy to final visit was 10.0 months and 10.5 monthsin hyperuricemia group and normal uric acid group respectively (P =0.85).In hyperuricemia group,complete remission was found in 5/19 cases (26.3％),slight abnormality in 10/19 cases (52.6％),severe abnormality in 4/19 cases (21.1％).Howe-ver,in normal uric acid group,complete remission was found in 19/31 cases (61.3 ％),10/31 cases (32.3 ％) of slight abnormalities and 2/31 cases (6.5％)of severe abnormalities.The non-remission cases in the hyperuricemia group were significantly higher than those in the normal uric acid group (x2 =7.878,P =0.042).Conclusions Urinary protein was higher in children with Henoch-Sch(o)nlein purpura nephritis complicated with hyperuricemia,the pathological of renal tubulointerstitium and glomerulus and the foot process change are more serious than those of patients with normal uric acid.Therefore,hyperuricemia may be used as a risk factor for poor prognosis.

Clinical manifestations and pathological characteristics of Henöch-Schönlein purpura nephritis combined with hyperuricemia in children / 中华实用儿科临床杂志

Objective@#To analyze the relationship of clinical manifestations and pathological characteristics of Henoch-Schönlein purpura nephritis combined with hyperuricemia in children.@*Methods@#A retrospective study was conducted in 50 children with Henoch-Schönlein purpura nephritis who hospitalized at Department of Nephrology, Affiliated Children′s Hospital, Capital Institute of Pediatrics from January 2014 to May 2018.The differences between the hyperuricemia group(19 cases)and the normal uric acid group(31 cases), were compared in age, sex, blood pressure, serum albumin, 24-hour urinary protein, serum creatinine, triglyceride, cholesterol, high density lipoprotein, low density lipoprotein, serum uric acid, estimated glomerular filtration rate, and renal pathological characteristics, and the short-term prognosis was analyzed.@*Results@#(1)The average urinary protein in the hyperuricemia group and the normal uric acid group was (91.67±90.37) mg/(kg·d) and (64.62±43.28) mg/(kg·d), respectively and the difference was statistically significant between the both groups(t=2.04, P=0.047); and the morbidity with massive proteinuria in hyperuricemia group and normal uric acid group was 18/19 cases(94.7%)and 17/31 cases(54.8%), respectively and the difference was statistically significant between the both groups(χ2=8.930, P=0.003). (2)In all cases, there were 4 cases of glomerular pathological grade Ⅱ, 43 cases of grade Ⅲ and 3 cases of grade Ⅳ.The pathological grading of hyperuricemia group and normal uric acid group was mainly grade Ⅲ, including 16/19 cases (84.2%) in hyperuricemia group and 27/31 cases (87.1%) in normal uric acid group, 4 cases of grade Ⅱ in normal uric acid group and 3 cases of grade Ⅳ in hyperuricemia group, the pathological grade of hyperuricemia group was relatively severe (χ2=7.358, P=0.025). There was no significant difference about the degree of global sclerosis and mesangial proliferation between hyperuricemia group and normal uric acid group(χ2=2.426, P=0.119, χ2=0.043, P=0.836, respectively); 7/19 cases (36.8%) had severe foot process lesions in hyperuricemia group, which was significantly higher than that in normal uric acid group [4/31 cases(12.9%)](χ2=3.934, P=0.047). In hyperuricemia group, tubulointerstitial lesions were found in 9/19 cases (47.4%) of (+ ) grade and 10/19 cases (52.6%) of (+ + ) grade, and 12/31 cases (38.7%) had normal tubulointerstitium in normal uric acid group, (+ )and (+ + )grade lesions were also less than those in the hyperuricemia group(χ2=10.694, P=0.005). The mean scores of tubular atrophy and interstitial fibrosis were significantly higher in hyperuricemia group than that in normal uric acid group(t=2.36, P=0.001). (3) The interval from renal biopsy to final visit was 10.0 months and 10.5 monthsin hyperuricemia group and normal uric acid group respectively (P=0.85). In hyperuricemia group, complete remission was found in 5/19 cases (26.3%), slight abnormality in 10/19 cases (52.6%), severe abnormality in 4/19 cases (21.1%). Howe-ver, in normal uric acid group, complete remission was found in 19/31 cases (61.3%), 10/31 cases (32.3%) of slight abnormalities and 2/31 cases (6.5%)of severe abnormalities.The non-remission cases in the hyperuricemia group were significantly higher than those in the normal uric acid group(χ2=7.878, P=0.042).@*Conclusions@#Urinary protein was higher in children with Henoch-Schönlein purpura nephritis complicated with hyperuricemia, the pathological of renal tubulointerstitium and glomerulus and the foot process change are more serious than those of patients with normal uric acid.Therefore, hyperuricemia may be used as a risk factor for poor prognosis.

Primary vesicoureteric reflux in 72 children / 中华实用儿科临床杂志

Objective@#To summarize the treatment and prognosis of children with primary vesicoureteric reflux (PVUR) and the correlation between PVUR and urinary tract infections(UTI).@*Methods@#The children with PVUR (72 cases) who were hospitalized at the Department of Nephrology and Urology of Children′s Hospital Affiliated to Capital Institute of Pediatrics from June 2007 to April 2018 were selected, and the clinical manifestations were summarized.@*Results@#A total of 72 patients (52 boys, 20 girls) were involved, and the median age at diagnosis was 8 months, in which 44 cases (61.1%) were less than 1 year old.There were 55 cases with UTI onset (76.4%), 94.5%(52/55 cases) with recurrent UTI(twice or more than twice) and 2 cases (2.8%) ended with renal failure.Refluxes were unilateral in 34 patients and bilateral in 38 patients.There were 110 ureters, in which 74 reflux ureters (67.3%) were identified as low-grade (Ⅰ-Ⅲ) PVUR, and 36 reflux ureters(32.7%) were high-grade (Ⅳ-Ⅴ) PVUR.Forty patients received conservative treatment, and significant differences of the remission rate were observed between group Ⅰ-Ⅱ grade PVUR(72.2%, 13/18 cases) and group Ⅲ-Ⅴ grade PVUR(32.5%, 13/40 cases)(χ2=7.92, P=0.005). Twenty-two patients (35 reflux ureters) underwent surgical treatment, in which 31 ureters were cured, and the remission rate was 88.6%.Ten patients with refluxes grade Ⅲ or above had no improvement after medical treatment, but the reflux was completely relieved after surgical treatment.@*Conclusions@#Children with recurrent UTI, especially less than 1 year-old, should be considered with PVUR.The conservative treatment could be prior for the patients with Ⅰ-Ⅱ grade PVUR.The surgical treatment could be chosen for those patients who suffered from high-grade PVUR, bilateral reflux or failed conservative treatment, especially with recurrent UTI, and reflux nephropathy could be reduced then.

Mycophenolate mofetil versus cyclosporine A in children with primary refractory nephrotic syndrome / 中华儿科杂志

Objective@#To compare the efficacy and safety of mycophenolate mofetil versus cyclosporine A in treating children with primary refractory nephrotic syndrome.@*Methods@#Conducted a prospective randomized controlled clinical trial in 62 pediatric patients (including 44 boys and 18 girls), age ranged from 2.1 to 17.0 years; 32 cases presented with frequently relapsing nephrotic syndrome (FRNS) and 30 cases presented with steroid-resistant nephrotic syndrome (SRNS), who were admitted to department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics from October 2013 to October 2015. The patients received either mycophenolate mofetil (20-30)mg/(kg·d) or cyclosporine A (3-5)mg/(kg·d) randomly, on the basis of prednisone treatment. Follow-up interview was conducted regularly for at least one year. Efficacy rate, relapse rate, time required for induction of remission, relapse-free period and prednisone dosage were compared between the two groups.@*Results@#(1) Renal histologic examination, which was available for 17 patients, revealed minimal change disease in 8 patients, mesangial proliferative glomerulonephritis (MsPGN) in five, membranous nephropathy in two, and focal segmental glomerulosclerosis (FSGS) in two. (2) Comparison of mycophenolate mofetil versus cyclosporine A in children with FRNS: There were 14 patients with FRNS in mycophenolate mofetil group and 18 patients with FRNS in cyclosporine A group respectively. The relapse rate (episodes/year) in cyclosporine A group was lower than that of mycophenolate mofetil group (1.0 (0.0, 1.0) vs. 1.0 (1.0, 3.0), Z=-2.405, P=0.016). The relapse-free period (months) in cyclosporine A group was longer than that of mycophenolate mofetil group (10.0 (5.7, 12.1) vs. 5.0 (1.0, 11.0), Z=-1.984, P=0.047). No significant difference in dosage of prednisone was found between cyclosporine A and mycophenolate mofetil groups when followed up for 1 year. (3) Comparison of mycophenolate mofetil versus cyclosporine A in children with SRNS: The efficacy rate was 6/14 in mycophenolate mofetil group and 13/16 in cyclosporine A group. The complete remission rate was 4/14 in mycophenolate mofetil group and 12/16 in cyclosporine A group (P<0.05). The time (months) required for induction of remission in cyclosporine A group was significantly shorter than that of mycophenolate mofetil group (1.0 (1.0, 2.0) vs. 3.0 (2.5, 4.0), Z=-2.529, P=0.011). No significant differences were found between the two groups with respect to relapse-free period and relapse rate. (4) Except that one patient developed hypertensive encephalopathy in cyclosporine A group, no other serious adverse events were recorded. There were no significant differences between two groups with respect to adverse events.@*Conclusion@#Our results indicated that both mycophenolate mofetil and cyclosporine A were effective in the treatment of children with refractory nephrotic syndrome. Cyclosporine A was superior to mycophenolate mofetil in preventing relapses in patients with FRNS and inducing complete remission in patients with SRNS. Although most patients were able to tolerate mycophenolate mofetil and cyclosporine A, but the toxicity and safety of cyclosporine A should be monitored closely.

Analysis of curative effect by Captopril in Henoch-Sch(o)nlein purpura nephritis characterized by mild proteinuria / 中华实用儿科临床杂志

Objective To explore the activation of renin-angiotensin system (RAS),efficiency and safety of Captopril,and the predictor of therapeutic activity for Henoch-Sch(o)nlein purpura nephritis (HSPN) characterized by mild proteinuria.Methods A total of 71 children who were hospitalized in Children's Hospital Affiliated to Capital Institute of Pediatrics from July 2014 to January 2017 were involved,with the diagnosis of HSPN and the characteristic of mild proteinuria.The cases were divided into 2 groups,one as Captopril group,the other as case control group.The patients were followed up for 6 months.Forty healthy children were assigned as healthy control group.Blood pressure,urinary protein excretion,levels of urinary angiotensinogen (AGT) and transforming growth factor β1 (TGF-β1),and the side effects of Captopril were surveyed.The therapeutic effects of these groups were analyzed by Kaplan-Meier survival curve.Results (1) Clinical characteristics:in the 71 cases,43 cases were male,28 cases were female,aged from 3 years to 14 years and 7 months.A total of 32 cases (45.1％) had manifested with isolated proteinuria,39 cases (54.9％) were with hematuria and proteinuria.The volume of 24 hours' urinary protein was 4.2-23.5 mg/(m2 · h) [median 9.6(7,12) mg/(m2 · h)] at the beginning.(2) The level of urinary AGT:the levels of urinary AGT in the children with HSPN were significantly higher than those of the healthy control group(Z =-3.010,P =0.003).(3) Curative effect:there was no significant difference in age,disease staging,mean arterial pressure(MAP),levels of urinary of proteinuria and estimated glomerular filtration rate (eGFR) between the patients with or without Captopril.The proteinuria was relieved in 88.57％ cases of Captopril group(35 cases),and the proportion was 80.55％ in the case control group(36 cases),and there was no significant difference between the 2 groups.The levels of proteinuria were decreased significantly in the children of Captopfil group 2 months after the enrollment,and there was a statistical significance (Z =2.010,P =0.044).But in the patients of each group,the levels of urinary protein excretion (Z =-2.127,P=0.030;Z=-2.639,P=0.010),TGF-β1(Z=-2.126,P=0.030;Z=-2.058,P=0.040) at theonset were significantly higher in the children with persistent proteinuria compared to those with remission of proteinuria completely,and there was a statistical significance.(4)Side effect:among 35 cases with therapy of Captopril,4 cases (11.42％) were verified to have adverse reaction (hypotension,dry cough and abnormal renal function),with mild symptom.Conclusion The overall prognosis of children of HSPN presenting as mild proteinuria are not improved completely by Captopril.The occurrence of adverse effects for Captopril is seldom and less severe.The level of urinary protein excretion,TGF-31 and AGT at the onset have some relevance with the prognosis of the patients of HSPN.

Advances in Study on Role of Cathepsin S in Irritable Bowel Syndrome / 胃肠病学

Irritable bowel syndrome(IBS)is a common functional intestinal disease,and its etiology and pathogenesis are not completely clear. The pathogenesis of IBS involves disturbed gastrointestinal motility,gut hypersensitivity,intestinal inflammation,immune dysfunction and brain-gut axis abnormality. Cathepsin S(CTSS)is a proteolytic enzyme widely distributed in various cell lysosomes,and participates in a variety of pathophysiological processes. Recent studies have shown that CTSS may be involved in the pathogenesis of IBS. This article reviewed the advances in study on role of CTSS in IBS.

Potential Regulatory Effects of Corticotropin-Releasing Factor on Tight Junction-Related Intestinal Epithelial Permeability are Partially Mediated by CK8 Upregulation.

BACKGROUND/AIMS: Intestinal permeability and stress have been implicated in the pathophysiology of irritable bowel syndrome (IBS). Cytokeratin 8 (CK8), for the first time, has been shown to mediate corticotropin-releasing factor (CRF)-induced changes in intestinal permeability in animal models of IBS. In this study, we investigated the regulatory effects of CRF on the permeability of human intestinal epithelial cells through the CK8-mediated tight junction. METHODS: The expression levels of corticotropin-releasing factor receptor 1 (CRFR1) and corticotropin-releasing factor receptor 2 (CRFR2) on the HT29 cell surface were determined by immunofluorescence, RT-PCR, and Western blotting. After treatment with 100 nM CRF for 72 h, the translocation of FITC-labelled dextran was measured in a transwell chamber; the structural changes of tight junctions were observed under transmission electron microscopy; the expression levels of CK8, F-actin and tight junction proteins ZO-1, claudin-1, and occludin were detected by immunoblotting and immunofluorescence. The activity of RhoA was detected by immunoprecipitation. Furthermore, the effects of CRF on intestinal epithelial permeability were examined in CK8-silenced HT29 cells, which were constructed by shRNA interference. RESULTS: CRF treatment increased FITC-labelled dextran permeability, caused the opening of tight junctions, induced increased fluorescence intensity of CK8 and decreased the intensities of ZO-1, claudin-1, and occludin, together with structural disruption. The expression levels of F-actin, occludin, claudin-1, and ZO-1 were downregulated. RhoA activity peaked at 30 min after CRF treatment. CRF-induced increased permeability, and downregulation of claudin-1 and occludin were not blocked by CK8 silencing. Nevertheless, CK8 silencing blocked the effects of CRF regarding the decrease in the expression levels of F-action and ZO-1 and increase in RhoA activity. CONCLUSION: CRF may increase intestinal epithelial permeability by upregulating CK8 expression, activating the RhoA signalling pathway, promoting intestinal epithelial actin remodelling, and decreasing the expression of the tight junction protein ZO-1. Other CK8-independent pathways may be involved in the downregulation of claudin-1 and occludin, which might also contribute to increased intestinal epithelial permeability.

Clinical analysis of Henoch-Sch(o)nlein purpura nephritis with mild proteinuria in children / 中华实用儿科临床杂志

Objective To analyze the clinical feature and prognosis of Henoch-Sch(o)nlein purpura nephritis (HSPN) with mild proteinuria in children.Methods The data of 78 HSPN children with mild proteinuria who were hospitalized in Children's Hospital Affiliated to Capital Institute of Pediatrics from September 2013 to September 2016 were retrospectively analyzed.All the cases were followed up.The clinical manifestation,histologic characteristics,treatment and outcome were analyzed,and the prognosis was compared between groups of different levels of proteinuria.Results (1) In the 78 cases,45 cases were male and 33 cases were female.The attack age range was from 3 years and 8 months to 14 years and 3 months,and the renal involvement occurred from 1 day to 60 months in courses of Hen(o)chSch(o)nlein purpura.(2)Twenty-seven cases were manifested with isolated proteinuria,and 51 cases were with hematuria and proteinuria.All the cases had normal kidney function while 2 cases had hypertension.Renal biopsy was performed in 9 cases,in which 6 cases were Ⅲ b,the other 3 cases were Ⅱ b.(3) Twelve cases were treated with regimen of immunosuppression and/or glucocorticoid.By the end of follow-up,the urinary analysis showed 46 cases (50.9％) had completely recovered,29 cases (37.2％)just had microscopic hematuria but no proteinuria,and 3 cases (3.8％) had obvious proteinuria.The renal involvement of 7 cases (9％) had been recurrent during the follow-up.(4) The time of recovery of proteinuria in the group with urinary protein ≤ 15 mg/kg(median:1 month) was less than that of the group with urinary protein ＞ 15 mg/kg(median:3 months),and the difference was significant (Z =-4.12,P =0.001),and 6 cases were found recurrent in the former group (10.9％) but 1 case(4.3％) in the latter group,and the difference was not significant (x2 =0.24,P =0.624).Conclusions The clinical characteristics of children with HSPN with mild proteinuria are not serious,and most of the cases had a favorable prognosis.However,some cases have protracted and recurrent courses which have serious pathological grade.So,urine analysis,long term follow-up,timely kidney biopsy and appropriate treatment are significant for HSPN with mild proteinuria.