[Treatment effectiveness and long-term prognosis of childhood-onset lupus nephritis].
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Objectives: To analyze the clinical characteristics, treatment effectiveness and long-term prognosis of childhood-onset lupus nephritis (LN), and to explore the risk factors for progression to end-stage renal disease (ESRD). Methods: In this retrospective study, the clinical data including general conditions, clinical manifestations, laboratory examinations, treatment, following up (till December 31st, 2020) and prognosis of 343 children with LN who were treated and followed up in the First Affiliated Hospital of Sun Yat-sen University from January 1, 2003 to December 31, 2019 were analyzed. Complete remission rates were compared between different pathological types according to renal biopsies and flare rates were compared between complete remission group and partial remission group according to the treatment effectiveness after 6 months of induction treatment. To investigate the risk factors of ESRD, the prognosis of flare and non-flare cases, and of cases with normal and elevated serum creatinine levels at baseline, was compared. Chi-squared tests were used for comparison between groups, and cumulative survival rate and renal survival rates were calculated by Kaplan-Meier survival analysis. Risk factors for ESRD were analyzed by COX regression model. Results: Among the 343 children, 68 were males (19.8%) and 275 were females (80.2%) with a median age of 13.0 (11.0, 16.0) years. Regarding the renal symptoms, 305 (88.9%) children had proteinuria and 245 (71.4%) had hematuria; while for extra-renal manifestations, 273 (79.6%) had anemia, 183 (53.4%) had rashes and 165 (48.1%) had fever. A total of 212 (61.8%) children had severely active SLE at initial presentation. After 6 months of induction treatment, the complete remission rate was 63.8% (219/343) and the partial remission rate was 27.1% (93/343). The complete remission rate was significantly higher in type Ⅰ and type Ⅱ LN compared to type Ⅳ LN (10/12 vs. 82/135 (60.7%), χ²=3.936, P=0.047). One hundred and ten children who achieved remission, including complete remission and partial remission, experienced renal flare with a flare rate of 35.3% and a mean time to flare was (43.2±28.4) months. There was no significant difference in flare rates between complete and partial remission group (36.1% (79/219) vs. 33.3% (31/93), χ²=3.394, P=0.065). The follow-up time of all the children was 60.4 (32.3, 100.9) months. During the follow-up period, 15 children died and the cumulative survival rates at 3, 5 and 10 years were 97.2%, 96.4% and 93.3%, respectively; 14 children progressed to ESRD and the cumulative renal survival rates at 3, 5, and 10 years were 99.2%, 97.1%, and 93.4%, respectively. COX multivariate analysis demonstrated that elevated serum creatinine at baseline, nephritic flare and nephrotic flare were independent risk factors for progression of ESRD (hazard ratio (HR)=3.575, 21.550 and 8.590, 95%CI 1.127-11.341, 2.394-194.027 and 1.042-70.823, P=0.031, 0.006, and 0.046, respectively). Conclusions: Children with LN are characterized by high SLE disease activity and multi-system involvement at onset. After 6 months of induction treatment, most of LN children could achieve clinical remission but some would experience renal flare. Nephritic flare, nephrotic flare and elevated serum creatinine at onset are independent risk factors for the progression of ESRD in children with LN.目的： 总结儿童狼疮性肾炎（LN）的临床特征并分析其治疗效果及远期预后，探讨LN患儿进展至终末期肾脏病（ESRD）的危险因素。 方法： 回顾性分析2003年1月至2019年12月于中山大学附属第一医院治疗并随访的343例LN患儿的一般情况、临床表现、实验室检查、治疗、随访（截至12月31日）和预后情况等临床资料。根据肾活检病理的不同分型比较其完全缓解率；根据诱导治疗6个月后缓解情况分为完全缓解组和部分缓解组比较其复发情况；按复发情况分为无复发组、蛋白尿型复发组和肾炎型复发组；按起病时血肌酐有无升高分为血肌酐正常组和血肌酐升高组。组间比较采用χ²检验，采用Kaplan-Meier生存分析计算患儿存活率及肾脏存活率，ESRD的危险因素采用COX比例风险回归模型进行分析。 结果： 343例LN患儿中男68例（19.8%）、女275例（80.2%），发病年龄为13.0（11.0，16.0）岁。LN患儿的肾脏表现中蛋白尿305例（88.9%）、血尿245例（71.4%）；肾外表现中贫血273例（79.6%）、皮疹183例（53.4%）和发热165例（48.1%）。212例（61.8%）患儿起病时为重度狼疮活动。LN患儿诱导治疗6个月后完全缓解率为63.8%（219/343），部分缓解率为27.1%（93/343）；Ⅰ和Ⅱ型患儿的完全缓解率高于Ⅳ型［10/12比60.7%（82/135），χ²=3.936，P=0.047］。共110例（35.3%）诱导缓解（完全缓解和部分缓解）的患儿出现复发，复发时间为（43.2±28.4）个月，79例为完全缓解后复发，31例为部分缓解后复发，完全缓解和部分缓解患儿的复发率差异无统计学意义［36.1%（79/219）比33.3%（31/93），χ²=3.394，P=0.065］。343例患儿随访时间为60.4（32.3，100.9）个月。随访期间共15例患儿死亡，LN患儿3、5、10年的累积存活率分别为97.2%、96.4%、93.3%；共14例患儿进展至ESRD，LN患儿的3、5、10年累积肾脏存活率分别为99.2%、97.1%、93.4%。COX多因素分析显示起病时血肌酐升高、肾炎型复发和蛋白尿型复发为进展至ESRD的独立危险因素（风险比=3.575、21.550、8.590，95%CI：1.127~11.341、2.394~194.027、1.042~70.823，P=0.031、0.006、0.046）。 结论： 儿童LN起病时SLE疾病活动度高，常为多系统受累，经6个月诱导治疗大多数LN患儿可达到临床缓解，但部分患儿诱导缓解后复发；肾炎型复发和蛋白尿型复发、起病时血肌酐升高为LN患儿进展至ESRD的独立危险因素。.Keywords:
Nephritis
Purpose We performed a systematic review and meta-analysis to compare response rates (complete remission plus partial remission) for nonsteroid immunosuppressant therapy to steroid-only immunosuppressant therapy in patients with membranous lupus nephritis. Methods A literature review was conducted from June 25, 2010 by querying PubMed, MEDLINE, and EMBASE databases. Inclusion criteria were trials containing remission data on patients with confirmed pure class V (Va and Vb) membranous lupus nephritis. The primary analysis evaluates response rates for regimens that contain at least one nonsteroid immunosuppressant therapy and steroid-only immunosuppressant therapy. A proportion meta-analysis using a DerSimonian-Laird random-effects model was performed. Data are reported as pooled proportions in percentages with 95% confidence intervals. Significant heterogeneity and/or bias were compensated for by trial exclusion. Results Twenty-four studies met inclusion criteria for meta-analysis, which yielded 34 groups of patients' data. Upon meta-analysis, the response rate for nonsteroid immunosuppressant therapy is higher than for steroids alone (81% [74%-87%] vs 60% [39%-79%]), even when compensating for significant heterogeneity and bias (76% [71%-81%] versus 60% [39%-79%]). Conclusion Nonsteroid immunosuppressant therapies in combination with steroids seem to be more effective than steroids alone for inducing partial or complete remission in patients with membranous lupus nephritis who have nephrotic proteinuria at baseline. This trial was not able to analyze adverse events, flares, relapses, or patient survival because of underreporting.
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Despite its widespread use, there are only a few published studies of the use of intravenous high dose pulse cyclophosphamide in systemic lupus nephritis. There are few data about the long-term efficacy and safety of this form of therapy. This study evaluates the clinical efficacy, toxicity, and effects on renal morphology of this regimen in patients with severe lupus nephritis followed prospectively over a five-year period. Twenty consecutive patients with severe active lupus nephritis were enrolled in a treatment regimen of six monthly intravenous pulses of cyclophosphamide (0.5 to 1 g/m2) together with high dose corticosteroid therapy which was rapidly tapered. Efficacy was assessed by improvement or stabilization of clinical, serologic and renal functional parameters. Repeat renal biopsies were performed in 15 patients. Potential toxicity related to therapy was documented. Over the first six months of treatment, this regimen resulted in improvement of clinical activity, lupus serology, stabilization of renal function and decreased proteinuria in 19/20 patients. Nephrotic syndrome remitted in 8/10 patients by one year. Over five years of follow-up, there were five treatment failures defined as a doubling of serum creatinine over baseline. At five years, 3 patients required renal replacement therapy. Elevated plasma creatinine at time of first biopsy, degree of proteinuria, histologic activity and chronicity were not statistically correlated with treatment failure. Patients who failed to respond to this treatment were, however, more likely to have diffuse proliferative lupus nephritis (WHO Class IV) lesions on initial biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)
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Whether and when is it possible to completely stop immunosuppression in patients with lupus nephritis is still poorly defined.An attempt to slowly and progressively eliminate steroids and immunosuppressive drugs was tried in 73 of 161 (45.3%) patients with lupus nephritis who achieved a stable clinical remission defined as normal serum creatinine, proteinuria <0.5g/24h, inactive urine sediment, and no clinical signs of extra-renal activity of SLE for at least 12 months.Twenty-one out of the 73 patients (28.7%) who met the criteria for withdrawal of treatment developed flares during the phase of progressive reduction of therapy and their treatment was reinforced. Twenty patients entered remission again; the last patient was lost to follow-up at achievement of partial remission. In the other 52 of the 73 patients (71.2%), it was possible to completely withdraw treatment. Of these, 32 patients (group A) did not resume therapy for the subsequent follow-up (median 101.8 months); the other 20 patients (group B) had at least one flare, in median 37 months after withdrawing therapy, and had to be retreated. At the last observation, after a median follow-up of 286 months, 10 of these 20 patients were off therapy. At the last observation, two patients in group A and two in group B had died, no patient of group A and two of group B had developed renal insufficiency (serum creatinine 2.5 and 3 mg/dl, respectively). Compared to patients in group B, group A patients received longer treatment (98.1 vs. 31.0 months; p=0.01), had longer remission (52.8 vs. 12.0 months; p=0.000) before withdrawal of therapy, and continued chloroquine after stopping therapy (52% vs. 10%; p=0.004). In comparison to patients who never stopped therapy, patients who were able to interrupt treatment had lower risk of chronic renal insufficiency (3.8% vs. 28.4%; p=0.000), end-stage renal disease (0 vs. 12.8%; p=0.01), arterial hypertension (32.7% vs. 66.9%; p=0.000) and cardiovascular events (11.5% vs. 27.5%; p=0.04).Complete withdrawal of therapy is feasible in selected patients who achieved stable remission after long-term treatment. The reduction of treatment must be done in a very gradual manner, progressively and under strict medical surveillance. The withdrawal of therapy allows the patients to reduce renal and extra-renal damage accrual. Treatment with chloroquine may help to maintain remission in patients who discontinue steroids and immunosuppressive drugs.
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The paper provides evidence and results of using new therapeutical treatment of glomerulonephritis, such as pulse-therapy with cyclophosphane, therapy with angiotension-converting enzyme (ACE) inhibitors or that with antihyperlipidemic agents. Based on much experience with pulse-therapy with cyclophosphane (over 100 patients with chronic glomerulonephritis (CGN) and lupus nephritis), it is concluded that this method is highly effective. Treating 57 patients with ACE inhibitors has shown that in CGN these drugs should be used only when taking into account their antihypertensive effect and capacity of lowering intraglomerular hypertension, as evidenced by the renal functional reserve, and diminishing proteinuria. The long-term (7-12 month) antihyperlipidemic therapy (diet and lovastatin) in 20 patients with CGN accompanied by the nephrotic syndrome caused a significant reduction in the concentration of serum cholesterol and proteinuria, a significant increase in serum albumin levels; remission of the nephrotic syndrome occurred in 9 patients; but better effects were observed in non-inflammatory nephropathies, such as membranous nephropathy, focal segmental glomerulosclerosis, and nephrosclerosis.
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Immunosuppressive treatment has changed the prognosis of Lupus nephritis over time, but improvement in prognosis is difficult to analyze in different historical periods, and should be better demonstrated in comparison with life expectancy of sex-and age-matched people. Long-term patient and renal survival of 90 patients diagnosed with Lupus nephritis at our center from 1968 to 2001 with a follow-up time of 14+/-8 years was retrospectively evaluated. Patient and kidney survival significantly increased over time. Multivariate analyses show that risks of patient and renal death decreased by 8% at each year of follow-up, and increased by more than 5 time in patients aged > 30 years at diagnosis. As only 14 patients were men, relative survival as compared to that of the sex- and age-matched general population of the Piedmont Region was calculated for the 76 women. Improvement in the survival of the cohort of women was seen at any time of follow-up: in particular, it was sharply lower in the first period (relative survival at 5, 10 and 15 years = 0.784, 0.665, and 0.620, respectively) and increased in the second (relative survival at 5, 10 and 15 years = 0.939, 0.921, and 0.850, respectively) nearly approaching that expected for the general population, i.e. 0.993, 0.983 and 0.967, respectively. Taken together, our data allow us to draw the conclusion that life expectancy in women with Lupus nephritis has improved over time, paralleling an improved awareness of the disease and a significant increase in steroid pulse therapy as induction/remission phase. Improvement in survival is for the first time demonstrated to cover the gap with life expectancy of the general population for women with Lupus nephritis.
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Vaso-occlusive events in pediatric sickle cell disease (SCD) may cause various renal complications and lead to renal failure. We describe the renal conditions that develop among young patients with SCD and the factors associated with the prevalence of these nephropathies.Medicaid medical and pharmacy claims for an 11-year period were used to identify 2194 pediatric patients with SCD (HbSS homozygous). Survival analysis identified the most significant predictors of acute kidney injury and chronic renal failure, using demographics, SCD severity and pain medication, comorbid hypertension, hematuria, and proteinuria as the initial covariates.Prevalence of renal complications in our cohort was found to be relatively low, predominantly hematuria (6.3%) and proteinuria (3.2%). The multivariable analysis indicated that earlier development of acute kidney injury was significantly associated with older age (adjusted hazard ratio [aHR] 1.16, confidence interval [CI] 1.06-1.27), preexisting hypertension (aHR 3.05, CI 1.09-8.60), and preexisting hematuria (aHR 2.87, CI 1.05-7.93). Earlier development of chronic renal failure was significantly associated with older age (aHR 1.20, CI 1.08-1.32), preexisting hematuria (aHR 4.67, CI 1.57-13.94), and preexisting proteinuria (aHR 8.25, CI 2.12-10.38).These prevalence findings are novel in the US SCD pediatric population. The predictors of nephropathies identified in these children confirm clinical expectations. In addition, they suggest not only that pediatric nephrologists should be consulted earlier in the treatment of patients with SCD who are diagnosed as having comorbid hypertension or who develop hematuria or proteinuria during the course of their SCD treatment but also that both hydroxyurea and angiotensin-converting enzyme inhibitor therapies may be better used in these cases.
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Imerslund-Najman-Gräsbeck anemia is an infrequent disease with an autosomal recessive pattern of inheritance. The characteristic anomaly is selective malabsorption of vitamin B12 by the ileal mucosa. Diagnosis rests on a positive family history and on the demonstration of megaloblastic anemia with proteinuria. The proteinuria is due to glomerular dysfunction with mesangial proliferation. Management rests on lifelong parenteral administration of vitamin B12. A case of Imerslund anemia with a favorable outcome under vitamin B12 treatment is reported.
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