Idiopathic nephrotic syndrome (INS) necessitates administration of corticosteroids or corticoid-sparing agents in 60% of the cases for prolonged periods resulting in serious adverse effects.
To avoid ...these complications, we investigated the efficacy and safety of mycophenolate mofetil (MMF) in our retrospective single-center study with 15 patients presenting with complicated courses of INS and aspired to estimate a cutoff level for mycophenolic acid-area under the curve (MPA-AUC) values, which can predict relapses with high sensitivity.
Seven of 15 patients stayed in remission while receiving MMF. Average frequency of relapses was 1.39 (0.28-2.5) per year. In case of relapses, patients had lower predose and estimated AUC0-12 levels of MPA (P = 0.02 and 0.001, respectively). Based on the results of receiver operating characteristic analysis, we consider an estimated MPA-AUC0-12 lower than 44.6 mg·h·L(-1) as a risk factor for future relapses (91% sensitivity, 57% specificity, P = 0.06) because the prevalence of relapse is significantly lower (0.07 versus 0.5, P = 0.02), if the estimated MPA-AUC0-12 is >44.6 mg·h·L(-1). During MMF administration, we did not detect any adverse event requiring discontinuation of treatment.
In conclusion, we demonstrate MMF as an alternative treatment for children with complicated INS to maintain remission without serious side effects. Furthermore, we propose a higher therapeutic target range of MPA-AUC0-12 (>45 mg·h·L(-1)) than used in transplanted children underlining the crucial role of therapeutic drug monitoring.
Childhood steroid-dependent (SDNS) and frequently relapsing (FRNS) nephrotic syndromes often require long-term immunosuppressive therapy to maintain remission. Successful discontinuation of ...maintenance therapy remains to be a challenge with these children. In the following article, we report our experience on patients after discontinuation of steroid-sparing immunosuppressive maintenance therapy (IT). Thereby, we retrospectively reviewed all patients between 2006 and 2016 with a relapsing course of steroid-sensitive nephrotic syndrome (SDNS or FRNS) treated with steroid-sparing maintenance immunosuppressive medication. Patient data of a total of 24 patients were recorded for a median time of 53.5 (11.2 - 112) months. In 11 patients, therapy was discontinued at physician's discretion. Thereafter, 8 of 11 patients (group A) relapsed after a median time of 2.21 (0.23 - 9.17) months, and IT was restarted. The remaining 3 patients (group B) maintained in long-term remission for a median time of 26.9 (17.7 - 32.1) months until the end of observation. Neither age, at initial episode nor at discontinuation or duration of IT, differed significantly between the groups of patients with relapse after discontinuation of IT, compared to those without. There was a trend towards a shorter relapse-free interval before discontinuation in group A than in group B (35.7 vs. 44.1 months). All patients who restarted IT again attained a stable remission until the last follow-up and did not show any further relapse. These results demonstrate that a failed discontinuation attempt does not put the patient's future remission at risk. .
Background
Deficiency of complement factor H-related plasma proteins and complement factor H autoantibody-positive hemolytic uremic syndrome (DEAP-HUS), which is characterized by the deficiency of ...complement-factor H-related (CFHR) plasma proteins and the subsequent formation of autoantibodies against complement factor H (CFH), has been reported to have an adverse outcome in one third of patients. Therapy options include prompt removal of antibodies by plasma exchange and immunosuppressive therapy. Recently, restoration of complement control using the monoclonal antibody eculizumab has been shown to be effective as first- and as second-line therapy in cases of therapy resistance or severe side effects of the applied therapy.
Diagnosis/treatment
Here, we report a 6-year-old girl with DEAP-HUS and first-line therapy with eculizumab under immunosuppressive therapy with glucocorticoids and mycophenolate mofetil (MMF). This therapy led to a prompt and sustained clinical recovery, to a stable reduction of complement activation, and to a rapid decline in autoantibody titer. A second increase in the autoantibody titer was successfully treated with methylprednisolone and the child remained in remission. After 8.3 months of sustained complement control and 4.5 months of stable antibody suppression, eculizumab was successfully discontinued without any sign of relapse.
Conclusions
To our knowledge, this is the first reported case of a child with DEAP-HUS treated with the combination of eculizumab and immunosuppression as first-line therapy avoiding any HUS- or therapy-related complications and resulting in prompt clinical recovery. Importantly, clinical remission is maintained after discontinuation of eculizumab under stable immunosuppression.
Background
Henoch-Schönlein purpura (HSP) is the most common vasculitis in childhood and traditionally considered as a self-limiting disease. However, renal involvement can unfavorably determine ...long-term prognosis. The reported regimens to treat HSP nephritis (HSPN) are diverse, indicating that the most effective treatment remains controversial.
Methods
This retrospective, single-center study involved 18 patients presenting with HSPN and nephrotic-range proteinuria. We aimed to investigate the efficacy and safety of mycophenolate mofetil (MMF) and identify a cut-off level for estimated mycophenolic acid area under the curve (eMPA-AUC
0-12h
) values, which can predict complete remission with high sensitivity.
Results
Despite prior insufficient therapeutic response to corticosteroids, 89% of patients showed a significant decrease in proteinuria after 1 month of MMF treatment. None of them relapsed during treatment; however, two children relapsed after discontinuation. Based on results of a receiver operating characteristic (ROC) analysis, an eMPA-AUC
0–12h
>56.4 mg*h/l was a predictor for complete remission within 3 months (80% sensitivity, 83.3% specificity,
p
= 0.035). During MMF administration, we encountered no adverse event requiring discontinuation of treatment.
Conclusion
Our study demonstrates that MMF is a safe and potentially effective secondary treatment option for children with HSPN to achieve and maintain long-term remission without serious side effects. To achieve complete remission within 3 months, resolve severe inflammatory glomerular lesions, and avoid progression to chronic kidney disease, we propose timely diagnosis and early initiation of MMF with an eMPA-AUC
0–12h
value of 56.4 mg*h/l.
Background
Asymptomatic hyperuricemia is frequently observed in pediatric kidney transplant recipients; symptomatic hyperuricemia, however, is a rare complication. Only few data are available in this ...patient population. We, therefore, investigated the prevalence of hyperuricemia and its association with kidney transplant function and blood pressure in a multicenter cohort of pediatric kidney transplant recipients.
Methods
This is a retrospective, observational multicenter registry study. All pediatric kidney transplant recipients in the CERTAIN database with at least one documented serum uric acid level and a follow‐up of 5 years posttransplant were eligible. We identified 151 patients with 395 measurements of serum uric acid. We calculated the prevalence of hyperuricemia, analyzed potential risk factors and clinical consequences such as elevated blood pressure and reduced estimated glomerular filtration rate (eGFR). Statistical analysis was performed using IBM SPSS Statistics 26.
Results
One hundred and ten of 395 (27.8%) serum uric acid levels were above 416 µmol/L (7.0 mg/dL), defined as the upper limit of normal. Univariate analysis showed a significant (p = .026) inverse association of serum uric acid with eGFR overtime. There was no significant association of serum uric acid concentrations with body mass index (z‐score), blood pressure (z‐score), or sex. No episodes of gout were documented.
Conclusion
This study shows that hyperuricemia is present in a considerable number of patients sometime after pediatric kidney transplantation and is associated with lower eGFR. Whether hyperuricemia contributes to faster decline of graft function or to the overall cardiovascular risk of these patients remains to be elucidated.
C3 glomerulonephritis (C3GN) is a rare but severe form of kidney disease caused by fluid-phase dysregulation of the alternative complement pathway. Causative mutations in complement regulating genes ...as well as auto-immune forms of C3GN have been described. However, therapy and prognosis in individual patients remain a matter of debate and long-term data are scarce. This also applies for the management of transplant patients as disease recurrence post-transplant is frequent. Here, we depict the clinical courses of two sisters with the unique combination of an identical, homozygous mutation in the
gene as well as autoantibodies with a clinical follow-up of more than 20 years. Interestingly, the sisters presented with discordant clinical courses of C3GN with normal kidney function in one (patient A) and end-stage kidney disease in the other sister (patient B). In patient B, eculizumab was administered immediately prior to and in the course after kidney transplantation, with the result of a stable graft function without any signs of disease recurrence. Comprehensive genetic work-up revealed no further disease-causing mutation in both sisters. Intriguingly, the auto-antibody profile substantially differed in both sisters: autoantibodies in patient A reduced the C3b deposition, while the antibodies identified in patient B increased complement activation and deposition of split products. This study underlines the concept of a personalized-medicine approach in complement-associated diseases after thorough evaluation of the individual risk profile in each patient.
IntroductionIdiopathic nephrotic syndrome is the most common glomerular disease in childhood with an incidence of 1.8 cases per 100 000 children in Germany. The treatment of the first episode implies ...two aspects: induction of remission and sustainment of remission. The recent Kidney Disease Improving Global Outcomes, American Academy of Pediatrics and German guidelines for the initial treatment of the first episode of a nephrotic syndrome recommend a 12-week course of prednisone. Despite being effective, this treatment is associated with pronounced glucocorticoid-associated toxicity due to high-dose prednisone administration over a prolonged period of time. The aim of the INTENT study (Initial treatment of steroid-sensitive idiopathic nephrotic syndrom in children with mycophenolate mofetil versus prednisone: protocol for a randomised, controlled, multicentre trial) is to show that an alternative treatment regimen with mycophenolic acid is not inferior regarding sustainment of remission, but with lower toxicity compared with treatment with glucocorticoids only.Methods and designThe study is designed as an open, randomised, controlled, multicentre trial. 340 children with a first episode of steroid-sensitive nephrotic syndrome and who achieved remission by a standard prednisone regimen will be enrolled in the trial and randomised to one of two treatment arms. The standard care group will be treated with prednisone for a total of 12 weeks; in the experimental group the treatment is switched to mycophenolate mofetil, also for a total of 12 weeks in treatment duration. The primary endpoint is the occurrence of a treated relapse within 24 months after completion of initial treatment.Ethics and disseminationEthics approval for this trial was granted by the ethics committee of the Medical Faculty of the University of Heidelberg (AFmu-554/2014). The study results will be published in accordance with the Consolidated Standards of Reporting Trials statement and the Standard Protocol Items: Recommendations for Interventional Trials guidelines. Our findings will be submitted to major international paediatric nephrology and general paediatric conferences and submitted for publication in a peer-reviewed, open-access journal.Trial registration numberDRKS0006547; EudraCT2014-001991-76; Pre-result.Date of registration30 October 2014; 24 February 2017.
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