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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.
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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.
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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.
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4.
Membrane versus centrifuge-based therapeutic plasma exchange: a randomized prospective crossover study
Hafer C, Golla P, Gericke M, Eden G, Beutel G, Schmidt JJ, Schmidt BM, De Reys S Kielstein JT
International Urology & Nephrology. 2016;48((1)):133-8.
Abstract
BACKGROUND Therapeutic plasma exchange (TPE) is either performed using a highly permeable filter with standard multifunctional renal replacement equipment (mTPE) or a centrifugation device (cTPE). Although both techniques are well established in clinical practice, performance of these two modes of TPE was never compared in a prospective randomized fashion. Thus we aimed to compare two commercially available therapeutic apheresis systems: mTPE (Octonova with Plasmaflo filter) and cTPE (Spectra Optia apheresis system). METHODS Twenty-one patients (age 51.6 +/- 13.5 years; 10 F/11 M; BMI 25.1 +/- 5.0 kg/m(2)) were enrolled in this randomized, prospective, paired, crossover study performed in the Hannover Medical School, Germany. First treatment (either mTPE or cTPE) was chosen by an online randomization list. The primary endpoints were plasma removal efficiency with 1.2x of the total plasma volume exchanged. Secondary endpoints were total amount of plasma substances removed, such as IgG and fibrinogen. Further, the treatment effect on platelet count and complications were evaluated. RESULTS Despite a comparable volume of the processed plasma, mTPE treatment time was 10.5 % longer than cTPE treatment time (p < 0.05), resulting in a 10 % lower plasma removal rate of the mTPE treatment. Both treatments were comparable in terms of decrease in median (IQR) IgG [pre-mTPE 5.34 (3.48-8.37), post-mTPE 1.96 (1.43-2.84) g/L; pre-cTPE 5.88 (3.42-8.84), post-cTPE 1.89 (1.21-3.52) g/L]. Also the median (IQR) amount of IgG removed in mTPE [13.14 (7.42-16.10) g] was not different from the cTPE treatment [9.30 (6.26-15.69) g]. This was also true for IgM removal. Platelet loss during mTPE was nearly twice as much as with cTPE (15 +/- 9 versus 7 +/- 9 %, p < 0.05). CONCLUSION Although the centrifugal procedures were conducted using flow rates that could easily be obtained using peripheral access, plasma removal efficiency was significantly higher and treatment time was significantly lower in cTPE as compared to mTPE. Despite this lower treatment time, the decline in markers of procedure efficacy was comparable. Especially in centers performing many procedures per year, cTPE in contrast to mTPE can reduce treatment time without compromising treatment efficacy.
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5.
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.
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6.
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.
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7.
Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis
Jayne DR, Gaskin G, Rasmussen N, Abramowicz D, Ferrario F, Guillevin L, Mirapeix E, Savage CO, Sinico RA, Stegeman CA, et al
Journal of the American Society of Nephrology. 2007;18((7):):2180-8.
Abstract
Systemic vasculitis associated with autoantibodies to neutrophil cytoplasmic antigens (ANCA) is the most frequent cause of rapidly progressive glomerulonephritis. Renal failure at presentation carries an increased risk for ESRD and death despite immunosuppressive therapy. This study investigated whether the addition of plasma exchange was more effective than intravenous methylprednisolone in the achievement of renal recovery in those who presented with a serum creatinine >500 micromol/L (5. 8 mg/dl). A total of 137 patients with a new diagnosis of ANCA-associated systemic vasculitis confirmed by renal biopsy and serum creatinine >500 micromol/L (5. 8 mg/dl) were randomly assigned to receive seven plasma exchanges (n = 70) or 3000 mg of intravenous methylprednisolone (n = 67). Both groups received oral cyclophosphamide and oral prednisolone. The primary end point was dialysis independence at 3 mo. Secondary end points included renal and patient survival at 1 yr and severe adverse event rates. At 3 mo, 33 (49%) of 67 after intravenous methylprednisolone compared with 48 (69%) or 70 after plasma exchange were alive and independent of dialysis (95% confidence interval for the difference 18 to 35%; P = 0. 02). As compared with intravenous methylprednisolone, plasma exchange was associated with a reduction in risk for progression to ESRD of 24% (95% confidence interval 6. 1 to 41%), from 43 to 19%, at 12 mo. Patient survival and severe adverse event rates at 1 yr were 51 (76%) of 67 and 32 of 67 (48%) in the intravenous methylprednisolone group and 51 (73%) of 70 and 35 of (50%) 70 in the plasma exchange group, respectively. Plasma exchange increased the rate of renal recovery in ANCA-associated systemic vasculitis that presented with renal failure when compared with intravenous methylprednisolone. Patient survival and severe adverse event rates were similar in both groups.
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8.
Chances of renal recovery for dialysis-dependent ANCA-associated glomerulonephritis
de Lind van Wijngaarden RA, Hauer HA, Wolterbeek R, Jayne DR, Gaskin G, Rasmussen N, Noël LH, Ferrario F, Waldherr R, Bruijn JA, et al
Journal of the American Society of Nephrology. 2007;18((7):):2189-97.
Abstract
In patients who have anti-neutrophil cytoplasm autoantibody (ANCA)-associated glomerulonephritis and are on dialysis at time of diagnosis, renal function is sometimes insufficiently restored by immunosuppressive treatment, which often coincides with potentially lethal adverse effects. This study investigated the clinical and histologic variables that determine the chances of dialysis independence, dialysis dependence, or death after 12 mo in these patients. Sixty-nine patients who had ANCA-associated glomerulonephritis and were dialysis dependent at diagnosis received uniform, standard immunosuppressive therapy plus either intravenous methylprednisolone or plasma exchange. Eleven clinical and histologic variables were assessed. Univariate and binary logistic regression analyses were performed. Predictive parameters were entered into a two-step binary logistic regression analysis to differentiate among the outcomes of dialysis independence, dialysis dependence, or death. The point at which the chance of therapy-related death exceeded the chance of dialysis independence was determined. The chance of recovery exceeded the chance of dying in most cases. Intravenous methylprednisolone as adjunctive therapy plus <18% normal glomeruli and severe tubular atrophy increased the chance of therapy-related death over the chance of dialysis independence. Plasma exchange treatment plus severe tubular atrophy and <2% normal glomeruli increased the chance of therapy-related death over that of dialysis independence. Even with ominous histologic findings, the chance of renal recovery exceeds the chance of therapy-related death when these patients are treated with plasma exchange as adjunctive therapy.
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9.
Plasma exchange or immunoadsorption in patients with rapidly progressive crescentic glomerulonephritis. A Swedish multi-center study
Stegmayr BG, Almroth G, Berlin G, Fehrman I, Kurkus J, Norda R, Olander R, Sterner G, Thysell H, Wikstrom B, et al
International Journal of Artificial Organs. 1999;22((2):):81-7.
Abstract
A therapeutic removal of antibodies may be achieved by immunoadsorption (IA) or by plasma exchange (PE). The aim of this prospective randomised study was to compare the efficacy of these different techniques with regard to treatment of patients with rapidly progressive glomerulonephritis (RPG) having at least 50% crescents. Forty-four patients with a RPG were included for treatment either by IA or PE (with albumin as substitution for removed plasma). All patients were additionally treated with immunosuppression. A median of 6 sessions of PEs were performed in 23 patients compared with 6 IAs in 21 patients. Goodpasture's syndrome (GP) was present in 6 patients (PE 3, IA 3). All of them started and ended in dialysis, two died. Among the remaining 38 patients (26 men, 12 women) 87% had antibodies to ANCA. Creatinine clearance for PE versus IA were at a median at start 17.1 and 19.8 ml/min, and at 6 months 49 and 49 ml/min, respectively. At 6 months 7 of 10 patients did not need dialysis (remaining: IA 0/5 and PE 2/5, n.s.). The extent of improvement did not differ between the groups. Three patients died during the observation period of 6 months (IA 2; PE 1, on HD). Although no difference was found between the IA or the PE group this study shows that the protocol used was associated with an improved renal function in most patients (except for Goodpasture's syndrome) whereas 70% of them could leave the dialysis program.
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10.
Therapy of lupus nephritis. A two-year prospective study
Doria A, Piccoli A, Vesco P, Vaccaro E, Marson P, De Silvestro G, Ossi E, Gambari P
Annales de Medecine Interne. 1994;145((5):):307-11.
Abstract
The aim of our study was to compare the efficacy of 3 different therapeutic protocols in the treatment of patients with WHO class IV lupus nephritis and normal renal function. We carried out a randomized prospective trial. The treatment programs consisted of a standard therapy regimen alone (protocol A), plus plasmapheresis (protocol B) or pulse methylprednisolone (protocol C), followed by a slow (protocols A and B) or fast (protocol C) prednisone tapering schedule. Statistical analysis was performed, using univariate survival analysis according to Kaplan Meier and Breslow's test to compare survival curves. Eighteen patients entered the study: 6 protocol A, 5 protocol B and 7 protocol C. No patients developed renal insufficiency. Moreover, no statistical differences in the probability of inducing partial or complete disease remission and in reducing 24-hour urinary protein excretion to < or = 2 g per day were observed among the groups. Protocols A and B were more effective in comparison with protocol C in decreasing 24-hour urinary protein excretion to < or = 0.5 g and < or = 0.2 g per day. In conclusion, a slow prednisone tapering schedule is more effective in reducing 24-hour urinary protein excretion to < or = 0.5 and < or = 0.2 g per day as compared with a fast prednisone tapering schedule, even if it is preceded by methylprednisolone pulse therapy.