Clinical presentation and prognosis in children over 10-year-old with primary nephrotic syndrome / 中华儿科杂志

Objective: To summary the clinical presentation and prognosis of primary nephrotic syndrome (PNS) in teenagers. Methods: The clinical data, renal pathological types and prognosis of 118 children over 10-year-old with PNS treated in the Department of Nephrology of the Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2010 to December 2020 were retrospectively analyzed, with 408 children ≤10-year-old as control group synchronously. Chi-square test was used to compare the difference of clinical types, pathologic types, response to steroids and tubulointerstitial changes between the groups. The teenagers with steroid resistant nephrotic syndrome (SRNS) were divided into initial non-responder group and late non-responder group. Kaplan-Meier method was used to compare the difference of persistent proteinuria, and Fisher's exact test for the histological types. Results: There were 118 children >10-year-old, including 74 males and 44 females, with the onset age of 12.1 (10.8, 13.4) years; and 408 children ≤10-year-old with the onset age of 4.5 (3.2, 6.8) years. The proportion of SRNS was significantly higher in patients >10-year-old than those ≤10-year-old (24.6% (29/118) vs. 15.9% (65/408), χ2=4.66, P=0.031). There was no statistical difference in the pathological types between >10-year-old and ≤10-year-old (P>0.05), with minimal change disease the most common type (56.0% (14/25) vs. 60.5% (26/43)). The percentage of cases with renal tubulointerstitial lesions was significantly higher in children >10-year-old compared to those ≤10-year-old (60.0% (15/25) vs. 23.3% (10/43), χ2=9.18, P=0.002). There were 29 cases presented with SRNS in PNS over 10-year-old, including 19 initial non-responders and 10 late non-responders. Analyzed by Kaplan-Meier curve, it was shown that the percentage of persistent proteinuria after 6 months of immunosuppressive treatments was significantly higher in initial non-responders than those of the late non-responders ((22±10)% vs. 0, χ2=14.68, P<0.001); the percentage of minimal change disease was significantly higher in patients of late non-responders than those of the initial non-responders (5/6 vs. 3/13, P=0.041). Of the 63 >10-year-old with steroid-sensitive nephrotic syndrome followed up more than one year, 38 cases (60.3%) had relapse, and 14 cases (22.2%) were frequent relapse nephrotic syndrome and steroid dependent nephrotic syndrome. Among the 45 patients followed up over 18-year-old, 22 cases (48.9%) had recurrent proteinuria continued to adulthood, 3 cases of SRNS progressed to kidney insufficiency, and one of them developed into end stage kidney disease and was administrated with hemodialysis. Conclusions: Cases over 10-year-old with PNS tend to present with SRNS and renal tubulointerstitial lesions. They have a favorable prognosis, but are liable to relapse in adulthood.

Therapeutic effect of mycophenolate mofetil or cyclophosphamide in children with Henoch-Schönlein purpura nephritis of different age groups / 中国当代儿科杂志

OBJECTIVES@#To investigate the difference in the therapeutic effect of mycophenolate mofetil (MMF) or cyclophosphamide (CTX) in children with Henoch-Schönlein purpura nephritis (HSPN) of different age groups.@*METHODS@#A retrospective analysis was conducted on the clinical data of 135 children with HSPN who were treated with MMF or CTX in the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics, from October 2018 to October 2020. According to the immunosuppressant used, they were divided into two groups: MMF group and CTX group, and according to the age, each group was further divided into two subgroups: ≤12 years and >12 years, producing four groups, i.e, the ≤12 years MMF subgroup (n=30), the >12 years MMF subgroup (n=15), the ≤12 years CTX subgroup (n=71), and the >12 years CTX subgroup (n=19). All children were followed up for at least 12 months, and the above groups were compared in terms of clinical outcomes and the incidence rate of adverse reactions.@*RESULTS@#There was no significant difference in the complete response rate between the MMF group and the CTX group after 3, 6, and 12 months of treatment (P>0.05). There were no significant difference in the complete response rate and the incidence rate of adverse reactions between the >12 years MMF subgroup and the ≤12 years MMF subgroup at 3, 6, and 12 months of treatment (P>0.05). The >12 years CTX subgroup had a significantly lower complete response rate than the ≤12 years CTX subgroup at 6 and 12 months of treatment (P<0.05). The >12 years CTX subgroup had a significantly higher incidence rate of adverse reactions than the >12 years MMF subgroup (P<0.05).@*CONCLUSIONS@#The efficacy and adverse reactions of MMF are not associated with age, but the efficacy of CTX is affected by age, with a higher incidence rate of adverse reactions. CTX should be selected with caution for children with HSPN aged >12 years.

Rare cause of coronary artery ectasia in children: A case report of methylmalonic acidemia with hyperhomocysteinemia.

Background: Methylmalonic acidemia (MMA) with hyperhomocysteinemia is caused by cobalamin deficiency, mainly due to disturbance of cobalamin C (cblC) metabolism. Its clinical manifestations involve many organs. However, cases of coronary artery ectasia have been rarely reported. Case presentation: Here, we report the case of a 4-year-old girl who was hospitalized mainly because of pallor, brown urine, and fatigue, followed by hypertension, renal insufficiency, hemolytic anemia, cardiac enlargement, cardiac insufficiency, and coronary artery ectasia. Thrombotic microangiopathy (TMA) was confirmed by renal pathological examination. Metabolic examination showed hyperhomocysteinemia and methylmalonic aciduria. Furthermore, genetic assessment confirmed MMACHC gene variant, which confirmed the final diagnosis of a cblC defect. Intramuscular injection of hydroxy-cobalamin, oral medications of betaine, levocarnitine, folic acid, and aspirin were administered. Three months later, the patient's condition was significantly improved. Anemia was corrected, and the renal function was normal. Heart size, cardiac function, and coronary artery structure completely returned to normal. Conclusion: The clinical manifestation of cblC deficiency is atypical. This critical condition may be associated with multiple organ involvement. A rare complication, coronary artery ectasia, can also occur. Early identification, careful evaluation, and appropriate treatment are crucially important for the improvement of this disease prognosis.

Clinical assessment of moderate-dose glucocorticoid in the treatment of recurrence of primary nephrotic syndrome in children: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVES@#To study the clinical effect and adverse drug reactions of different doses of glucocorticoid (GC) in the treatment of children with recurrence of steroid-sensitive nephrotic syndrome (SSNS).@*METHODS@#A total of 67 children who were hospitalized and diagnosed with SSNS recurrence in the Department of Nephrology, Children's Hospital, Capital Institute of Pediatrics, from November 2017 to December 2019 were enrolled. They were randomly divided into a moderate-dose GC group (32 children) and a full-dose GC group (35 children). The two groups were compared in terms of urinary protein clearance, recurrence rate within 6 months, and incidence rate of GC-associated adverse reactions.@*RESULTS@#There was no significant difference in the urinary protein clearance rate between the moderate-dose GC and full-dose GC groups (91% vs 94%, P>0.05). There was also no significant difference in the recurrence rate within 6 months between the two groups (41% vs 36%, P>0.05). At 6 months of follow-up, compared with the full-dose GC group, the moderate-dose GC group had a significantly lower cumulative dose of prednisone [(87±18) mg/kg vs (98±16) mg/kg, P=0.039] and a significantly lower proportion of children with an abnormal increase in body weight (6% vs 33%, P=0.045). The logistic regression analysis showed that prednisone dose ≥10 mg/alternate day at enrollment was a risk factor for recurrence within 6 months in children with SSNS (P=0.018).@*CONCLUSIONS@#For children with SSNS recurrence, moderate-dose GC has similar effects to full-dose GC in the remission induction rate and the recurrence rate within 6 months, with a lower cumulative dose and fewer GC-associated adverse reactions within 6 months than full-dose GC.

Efficacy and safety of mycophenolate mofetil versus cyclophosphamide in the treatment of Henoch-Schönlein purpura nephritis with nephrotic-range proteinuria in children: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVE@#To study the efficacy and safety of mycophenolate mofetil (MMF) versus cyclophosphamide (CTX) in the treatment of children with Henoch-Schönlein purpura nephritis (HSPN) and nephrotic-range proteinuria.@*METHODS@#A prospective clinical trial was conducted in 68 pediatric patients who were admitted to the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics and who were diagnosed with HSPN and nephrotic-range proteinuria from August 2016 to November 2019. The patients were randomly divided into two groups:MMF treatment (@*RESULTS@#At months 3, 6, and 12 of treatment, there was no significant difference in the complete remission rate and the response rate between the MMF treament and CTX treatment groups (@*CONCLUSIONS@#MMF and CTX have similar efficacy and safety in the treatment of HSPN children with nephrotic-range proteinuria.

High-throughput quantification of protein structural change reveals potential mechanisms of temperature adaptation in Mytilus mussels.

BACKGROUND: Temperature exerts a strong influence on protein evolution: species living in thermally distinct environments often exhibit adaptive differences in protein structure and function. However, previous research on protein temperature adaptation has focused on small numbers of proteins and on proteins adapted to extreme temperatures. Consequently, less is known about the types and quantity of evolutionary change that occurs to proteins when organisms adapt to small shifts in environmental temperature. In this study, these uncertainties were addressed by developing software that enabled comparison of structural changes associated with temperature adaptation (hydrogen bonding, salt bridge formation, and amino acid use) among large numbers of proteins from warm- and cold-adapted species of marine mussels, Mytilus galloprovincialis and Mytilus trossulus, respectively. RESULTS: Small differences in habitat temperature that characterize the evolutionary history of Mytilus mussels were sufficient to cause protein structural changes consistent with temperature adaptation. Hydrogen bonds and salt bridges that increase stability and protect against heat-induced denaturation were more abundant in proteins from warm-adapted M. galloprovincialis compared with proteins from cold-adapted M. trossulus. These structural changes were related to deviations in the use of polar and charged amino acids that facilitate formation of hydrogen bonds and salt bridges within proteins, respectively. Enzymes, in particular those within antioxidant and cell death pathways, were over-represented among proteins with the most hydrogen bonds and salt bridges in warm-adapted M. galloprovincialis. Unlike extremophile proteins, temperature adaptation in Mytilus proteins did not involve substantial changes in the number of hydrophobic or large volume amino acids, nor in the content of glycine or proline. CONCLUSIONS: Small shifts in organism temperature tolerance, such as that needed to cope with climate warming, may result from structural and functional changes to a small percentage of the proteome. Proteins in which function is dependent on large conformational change, notably enzymes, may be particularly sensitive to temperature perturbation and represent foci for natural selection. Protein temperature adaptation can occur through different types and frequencies of structural change, and adaptive mechanisms used to cope with small shifts in habitat temperature appear different from mechanisms used to retain protein function at temperature extremes.

A prospective, randomized, controlled clinical study of Huai Qi Huang granules in treatment of childhood primary nephrotic syndrome / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the efficacy of Huai Qi Huang granules in the treatment of childhood primary nephrotic syndrome.</p><p><b>METHODS</b>Between July 2009 and December 2011, patients who were admitted and diagnosed for the first time as childhood primary nephrotic syndrome were randomized into a treatment group (Huai Qi Huang granules plus glucocorticoid; n=23) and a control group (glucocorticoid alone; n=19) for a prospective study. The two groups were compared for regression time of edema, time to urinary protein clearance, relapse rate, incidence of infection, dosage of glucocorticoid, and humoral and cellular immunological indicators.</p><p><b>RESULTS</b>There were no significant differences in regression time of edema, time to urinary protein clearance, and relapse rate between the treatment and control groups (P>0.05). The treatment group had significantly lower incidence of infection and daily dose of glucocorticoid (at month 6) than the control group (P<0.05). Humoral and cellular immunological indicators showed no significant differences between the two groups (P>0.05). No Huai Qi Huang-related adverse events were observed in this study.</p><p><b>CONCLUSIONS</b>Huai Qi Huang granules treatment can reduce the dose of glucocorticoid and the incidence of infection in children with primary nephrotic syndrome and has a favourable safety.</p>

Application of plasma clearance of iohexol in evaluating renal function in chinese children with chronic kidney disease / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the accuracy of plasma clearance of iohexol (PCio) for glomerular filtration rate (GFR) measurement in Chinese children with chronic kidney disease (CKD) and assess the feasibility of single-blood-sample method or dried capillary blood spots in determining the PCio.</p><p><b>METHODS</b>Totally 45 CKD children were included,in whom the (99m) Technetium-diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) plasma clearance and iohexol plasma clearance were simultaneously determined. Blood samples were obtained 2,4,and 5 hours after injection. In addition, we also evaluated the efficacy of single blood sample method and dried blood spots method in iohexol plasma clearance.</p><p><b>RESULTS</b>Forty-five CKD children completed the iohexol plasma clearance and thirty-six children completed the (99m)Tc-DTPA plasma clearance at the same time among them. Thirteen children finished the iohexol dried blood spot clearance. The correlation coefficient between (99m)Tc-DTPA plasma clearance and iohexol plasma clearance was 0.941 and the bias was (6.53 ± 11.6) ml/ (min·1.73 m²), and the intraclass correlation coefficient (ICC) was high (ICC=0.947). The correlation between iohexol single-sample plasma clearance and double samples was also strong (r=0.958), with the bias being (4.26 ± 9.06)ml/(min·1.73 m²) and the ICC being 0.970. The iohexol clearance by dried blood spots showed a good correlation with the serum iohexol clearance (r=0.950), with the bias still being small [(0.48 ± 10.89)ml/(min·1.73 m²)].</p><p><b>CONCLUSIONS</b>Iohexol plasma clearance has satisfactory agreement with (99m)Tc-DTPA plasma clearance and can be used as an ideal method to measure GFR in CKD children. The single-sample method and dried blood spots method make iohexol plasma clearance more convenient and practical.</p>

Study on the mechanism of reversal effect of Curcuma Wenyujin on MDR of SGC7901/VCR / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the mechanism of reversal effect of Curcuma Wenyujin n-Butyl alcohol extract (CWNAE) on multiple drugs resistance (MDR) of SGC7901/VCR cells.</p><p><b>METHODS</b>SGC7901/VCR cells were co-culured with different concentrations CWNAE (80, 40, and 20 μg/mL) and Verapamil (VP, 10 μg/mL) for 24 h, and then acted with Adriamycin (ADM) for 1, 2, and 4 h, respec- tively. SGC7901/VCR cells with no intervention were taken as the vehicle control group. SGC7901/VCR cells treated with ADM alone were taken as the control group. The effect of CWNAE on intracellular ADM concentration was detected by flow cytometry (FCM). Cells were treated as mentioned before without any intervention of ADM. SGC7901/VCR with no ADM intervention were taken as the control group. The effect of CWNAE on the expression of P-glycoprotein (P-gp), lung resistance protein (LRP), and glu- cosylceramide synthase (GCS) was studied by Western blot. The effect of CWNAE on the location and expression quantity of P-gp was further illustrated by immunohistochemistry (IHC).</p><p><b>RESULTS</b>Compared with the ADM group, the expression ratio obviously increased in the W80, W40, W20, and VP10 groups with statistical difference (all P < 0.05). The comparative expression quantity of P-gp, GCS, and LRP in SGC7901/VCR cells was obviously higher than that of non-MDR with statistical difference (all P < 0.05). The expression quantity of P-gp and GCS could be obviously down-regulated by 80 and 40 μg/mL CWN- AE, and 10 μg/mL VP, with no effect on the expression of LRP. Results of IHC proved that P-gp was mainly expressed on the cytomembrane or in the plasma, and it was also expressed on the nuclear membrane. P-gp in different locations could all be down-regulated by CWNAE.</p><p><b>CONCLUSIONS</b>CWNAE could reverse the MDR of SGC7901/VCR cell line probably by inhibiting the expression of P-gp and GCS. CWNAE had no effect on LRP that also highly expressed on SGC7901/VCR. So we supposed that CWNAE could become a potential drug to reverse MDR of highly expressed P-gp and GCS.</p>

Influence of high- and low-osmolality contrast media on renal function in children / 中华儿科杂志

<p><b>OBJECTIVE</b>To compare the effects of different contrast media on the renal function in children, and to investigate the prophylactic efficacy of hydration.</p><p><b>METHODS</b>Sixty patients on whom either intravenous pyelography (IVP) or enhanced CT scan was required were divided into high osmolality contrast media (HOCM) group (n = 27) and low osmolality contrast media (LOCM) group (n = 33), and each group was randomly subdivided into hydration group (HG) and non-hydration group (NHG). In HOCM group, HG had 14 cases and NHG had 13 cases; while in LOCM group, HG had 18 cases and NHG had 15 cases. A 1/5-tonic solution at a dose of 20 ml/kg was intravenously given immediately after the exposure to a contrast medium within 3 hours in the HG, while the NHG cases were not given any infusion.</p><p><b>RESULTS</b>There were no significant difference between HG and NHG in baseline serum creatinin (SCr) and creatinin clearance (Ccr). After exposure, in HOCM group, SCr of NHG (59.71 +/- 12.49) micromol/L significantly increased as compared with baseline (49.91 +/- 6.09) micromol/L (P < 0.05), while Ccr (97.81 +/- 15.10)ml/(min x 1.73 m(2)) decreased compared with baseline (71.33 +/- 7.51) ml/(min x 1.73 m(2)) (P < 0.05). No significant changes of SCr and Ccr were observed in the HG before (48.37 +/- 7.11) micromol/L, (99.81 +/- 15.41) ml/(min x 1.73 m(2)) and after (49.63 +/- 6.84) micromol/L, (88.29 +/- 12.75) ml/(min x 1.73 m(2)) (P > 0.05) the exposure to contrast medium. Contrast medium-associated nephropathy (CAN) was found in 3 cases in NHG (23.1%, 3/13) but none in HG (P > 0.05). In the LOCM group, there was no significant difference in SCr and Ccr before and after the exposure to the contrast media. The incidence of CAN was 6.7% (1/15) in the NHG and 11.1% (2/18) in the HG (P > 0.05). The average increase of SCr in HOCM group was significantly higher than that in LOCM group (Z = -2.42, P < 0.05). The average decrease of Ccr in HOCM group was significantly higher than that in LOCM group (Z = -2.83, P < 0.05). The SCr and Ccr of the 6 CAN cases in both HOCM and LOCM groups returned to baseline level within 2 weeks.</p><p><b>CONCLUSIONS</b>(1) Children can develop reversible CAN after the exposure to high or low osmolality contrast medium. (2) The high osmolality contrast medium seemed to have more serious toxicity in renal function than low osmolality contrast medium. (3) The prophylactic use of hydration can effectively prevent CAN in patients who will expose to high osmolality contrast medium. (4) Children can develop reversible CAN after the exposure to low osmolality contrast medium even after hydration.</p>