1.
Management of Steroid-Resistant Nephrotic Syndrome in Children
Sachdeva S, Khan S, Davalos C, Avanthika C, Jhaveri S, Babu A, Patterson D, Yamani AJ
Cureus. 2021;13(11):e19363
Abstract
Nephrotic syndrome (NS) affects 115-169 children per 100,000, with rates varying by ethnicity and location. Immune dysregulation, systemic circulating substances, or hereditary structural abnormalities of the podocyte are considered to have a role in the etiology of idiopathic NS. Following daily therapy with corticosteroids, more than 85% of children and adolescents (often aged 1 to 12 years) with idiopathic nephrotic syndrome have full proteinuria remission. Patients with steroid-resistant nephrotic syndrome (SRNS) do not demonstrate remission after four weeks of daily prednisolone therapy. The incidence of steroid-resistant nephrotic syndrome in children varies between 35 and 92 percent. A third of SRNS patients have mutations in one of the important podocyte genes. An unidentified circulating factor is most likely to blame for the remaining instances of SRNS. The aim of this article is to explore and review the genetic factors and management of steroid-resistant nephrotic syndrome. An all language literature search was conducted on MEDLINE, COCHRANE, EMBASE, and Google Scholar till September 2021. The following search strings and Medical Subject Headings (MeSH) terms were used: "Steroid resistance", "nephrotic syndrome", "nephrosis" and "hypoalbuminemia". We comprehensively reviewed the literature on the epidemiology, genetics, current treatment protocols, and management of steroid-resistant nephrotic syndrome. We found that for individuals with non-genetic SRNS, calcineurin inhibitors (cyclosporine and tacrolimus) constitute the current mainstay of treatment, with around 70% of patients achieving full or partial remission and an acceptable long-term prognosis. Patients with SRNS who do not react to calcineurin inhibitors or other immunosuppressive medications may have deterioration in kidney function and may develop end-stage renal failure. Nonspecific renal protective medicines, such as angiotensin-converting enzyme inhibitors, angiotensin 2 receptor blockers, and anti-lipid medications, slow the course of the illness. Recurrent focal segmental glomerulosclerosis in the allograft affects around a third of individuals who get a kidney transplant, and it frequently responds to a combination of plasma exchange, rituximab, and increased immunosuppression. Despite the fact that these results show a considerable improvement in outcome, further multicenter controlled studies are required to determine the optimum drugs and regimens to be used.
2.
Combined rituximab and plasmapheresis or plasma exchange for focal segmental glomerulosclerosis in adult kidney transplant recipients: a meta-analysis
Hansrivijit P, Ghahramani N
Int Urol Nephrol. 2020
Abstract
PURPOSE To demonstrate the efficacy of combined rituximab and plasmapheresis (PP)/plasma exchange (PE) therapy for focal segmental glomerulosclerosis in transplanted kidneys (ptFSGS). METHODS We searched MEDLINE, SCOPUS, and Cochrane Library for eligible publications. Only observational studies or clinical trials containing patients' age > 18 years were included for full-text extraction. RESULTS A total of eight observational studies (n = 85) were included in meta-analyses. With a median follow-up of 18 months (IQR 4.4), combination therapy of RTX-PP/PE in patients with ptFSGS resulted in overall remission rate of 72.7% (95% CI 52.3-86.6%) with a significant reduction of proteinuria and serum creatinine levels. Complete remission was 41.0%, while partial remission was 31.7%. The mean difference of serum creatinine levels between pre- and post-treatment was - 0.65 mg/dL (95% CI - 1.15 to - 0.14). The mean difference of the degree of proteinuria between pre- and post-treatment was - 4.79 g/day (95% CI - 7.02 to - 2.56). Subgroup analyses were performed after adjusted for study year, type of intervention, and primary pre-transplant lesion. Patients with recurrent FSGS tended have lesser reduction in the degree of proteinuria compared to patients with de novo FSGS. Incidence of serious adverse events with combined RTX-PP/PE therapy was 0.12 event/year. CONCLUSION We conclude that combined RTX-PP/PE therapy may be considered as an alternative treatment of ptFSGS in achieving remission by lowering proteinuria and serum creatinine levels. However, the efficacy of combined RTX-PP/PE therapy must be confirmed in randomized-controlled trials.
3.
The role of plasma exchange in treating post-transplant focal segmental glomerulosclerosis: a systematic review and meta-analysis of 77 case-reports and case-series
Kashgary A, Sontrop JM, Li L, Al-Jaishi AA, Habibullah ZN, Alsolaimani R, Clark WF
Bmc Nephrology. 2016;17((1)):104.
Abstract
BACKGROUND Evidence on the role of plasma exchange for treating recurrent post-transplant focal segmental glomerulosclerosis (FSGS) comes largely from individual cases and uncontrolled series. We conducted a systematic review and meta-analysis to estimate the remission rate after treatment with plasma exchange, and to determine if remission varied with patient or treatment characteristics. METHODS We searched MEDLINE, EMBASE, Science Citation Index Expanded, and the Conference Proceedings Citation Index (Science and BIOSIS) for studies of patients with post-transplant recurrent FSGS who were treated with plasma exchange after recurrence (1950-2012). Of 678 studies screened, 77 met our inclusion criteria: 34 case reports (45 patients) and 43 case series (378 patients). We extracted patient-level data from each study and used random-effects models to calculate remission, defined as proteinuria <3.5 g/day (partial) or <0.5 g/day (complete). RESULTS The overall remission rate in 423 patients with outcome data was 71 % (95 % CI: 66 % to 75 %). In 235 patients with data on age, remission was similar for adults and children: 69.1 % (95 % CI: 59.6 % to 77.2 %) and 70.2 % (95 % CI: 61.1 % to 77.9 %). Males were more likely to achieve remission (OR = 2.85; 95 % CI: 1.44 to 5.62) and patients treated within 2 weeks of recurrence showed a trend towards higher likelihood of remission (OR = 2.16; 95 % CI: 0.93 to 5.01). Proteinuria >7 g/day at recurrence was inversely associated with remission (OR = 0.43; 95 % CI: 0.19 to 0.97). Age and type of kidney transplant (living vs. deceased) did not associate with remission. CONCLUSION In this systematic review of patients with recurrent post-transplant FSGS, 71 % of patients achieved full or partial remission after treatment with plasma exchange; however, extensive missing data and lack of a control group limit any conclusions on causality.
4.
Plasma exchange for renal vasculitis and idiopathic rapidly progressive glomerulonephritis: a meta-analysis
Walsh M, Catapano F, Szpirt W, Thorlund K, Bruchfeld A, Guillevin L, Haubitz M, Merkel PA, Peh CA, Pusey C, et al
American Journal of Kidney Diseases. 2011;57((4):):566-74.
Abstract
BACKGROUND Plasma exchange may be effective adjunctive treatment for renal vasculitis. We performed a systematic review and meta-analysis of randomized controlled trials of plasma exchange for renal vasculitis. STUDY DESIGN Systematic review and meta-analysis of articles identified from electronic databases, bibliographies, and studies identified by experts. Data were abstracted in parallel by 2 reviewers. SETTING & POPULATION Adults with idiopathic renal vasculitis or rapidly progressive glomerulonephritis. SELECTION CRITERIA FOR STUDIES Randomized controlled trials that compared standard care with standard care plus adjuvant plasma exchange in adult patients with either renal vasculitis or idiopathic rapidly progressive glomerulonephritis. INTERVENTION Adjuvant plasma exchange. OUTCOME Composite of end-stage renal disease or death. RESULTS We identified 9 trials including 387 patients. In a fixed-effects model, the pooled RR for end-stage renal disease or death was 0.80 for patients treated with adjunctive plasma exchange compared with standard care alone (95% CI, 0.65-0.99; P = 0.04). No significant heterogeneity was detected (P = 0.5; I(2) = 0%). The effect of plasma exchange did not differ significantly across the range of baseline serum creatinine values (P = 0.7) or number of plasma exchange treatments (P = 0.8). The RR for end-stage renal disease was 0.64 (95% CI, 0.47-0.88; P = 0.006), whereas the RR for death alone was 1.01 (95% CI, 0.71-1.4; P = 0.9). LIMITATIONS Although the primary result was statistically significant, there is insufficient statistical information to reliably determine whether plasma exchange decreases the composite of end-stage renal disease or death. CONCLUSIONS Plasma exchange may decrease the composite end point of end-stage renal disease or death in patients with renal vasculitis. Additional trials are required given the limited data available.
5.
Interventions for renal vasculitis in adults: a systematic review
Walters GD, Willis NS, Craig JC
BMC Nephrology. 2010;11((1):):Article Number 12.
Abstract
Background: Renal vasculitis presents as rapidly progressive glomerulonephritis and comprises of a group of conditions characterised by acute kidney failure, haematuria and proteinuria. Treatment of these conditions involves the use of steroid and non-steroid agents with or without adjunctive plasma exchange. Although immunosuppression has been successful, many questions remain unanswered in terms of dose and duration of therapy, the use of plasma exchange and the role of new therapies. This systematic review was conducted to determine the benefits and harms of any intervention for the treatment of renal vasculitis in adults. Methods: We searched the Cochrane Central Register of Controlled Trials, the Cochrane Renal Group Specialised Register, MEDLINE and EMBASE to June 2009. Randomised controlled trials investigating any intervention for the treatment of adults were included. Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as risk ratio with 95% confidence intervals for dichotomous outcomes or mean difference for continuous outcomes. Results: Twenty two studies (1674 patients) were included. Plasma exchange as adjunctive therapy significantly reduces the risk of end-stage kidney disease at 12 months (five studies: RR 0.47, CI 0.30 to 0.75). Four studies compared the use of pulse and continuous administration of cyclophosphamide. Remission rates were equivalent but pulse treatment causes an increased risk of relapse (4 studies: RR 1.79, CI 1.11 to 2.87) compared with continuous cyclophosphamide. Azathioprine has equivalent efficacy as a maintenance agent to cyclophosphamide with fewer episodes of leukopenia. Mycophenolate mofetil may be equivalent to cyclophosphamide as an induction agent but resulted in a higher relapse rate when tested against Azathioprine in remission maintenance. Rituximab is an effective remission induction agent. Methotrexate or Leflunomide are potential choices in remission maintenance therapy. Oral co-trimoxazole did not reduce relapses significantly in Wegener's granulomatosis. Conclusions: Plasma exchange is effective in patients with severe A.