Relapse Of Proteinuria Research Articles

Levamisole therapy in children with frequently relapsing and steroid-dependent nephrotic syndrome: a single-center experience.

IntroductionNumerous studies suggest that levamisole, an antihelmintic agent with an immunomodulatory effect, reduces the number of relapses in children with frequently relapsing and steroid-dependent nephrotic syndrome (FRNS/SDNS). The aim of the study was to present a single center’s experience in treatment of FRNS and SDNS with levamisole.Material and methodsAmong 72 children with FRNS/SDNS treated in our department with levamisole in the years 1984-2011 we studied in detail 53 patients (mean age: 6.5 ±3.0 years), in whom the medication was administered for at least 6 months. In these 53 patients we evaluated: the course of the disease before levamisole, the renal biopsy result, medications used, prednisone dose on levamisole initiation, duration of levamisole treatment, time to first relapse and number of relapses on levamisole, and levamisole side effects.ResultsThe duration of nephrotic syndrome was 3.4 ±2.9 years, and the number of relapses before levamisole treatment was 6.0 ±3.4. The dose of prednisone on initiation of levamisole treatment was 1.2 ±0.6 mg/kg/24 h, and the duration of levamisole treatment was 15.0 ±7.3 months. During levamisole treatment proteinuria relapsed in 34/53 (64.2%) children, and the time to first relapse was 8.8 ±8.1 months. During levamisole therapy relapses of the disease decreased significantly (2.7 ±2.0 vs. 1.8 ±2.1 relapses/year, p = 0.02). Time to first relapse correlated with total number of relapses (R = –0.59, p < 0.001) and number of relapses in one year during levamisole treatment (R = –0.60, p < 0.001).ConclusionsLevamisole is effective in reducing the number of relapses in children with frequently relapsing and steroid-dependent nephrotic syndrome. Early relapse of proteinuria on levamisole treatment in children with FRNS/SDNS suggests low efficacy of further treatment.

What is a reflex? A guide for understanding disorders of consciousness.

Uncertainty in diagnosing disorders of consciousness, and specifically in determining whether consciousness has been lost or retained, poses challenging scientific and ethical questions. Recent neuroimaging-based tests for consciousness have cast doubt on the reliability of behavioral criteria in assessing states of consciousness and generate new questions about the assumptions used in formulating coherent diagnostic criteria. The reflex, a foundational diagnostic tool, offers unique insight into these disorders; behaviors produced by unconscious patients are thought to be purely reflexive, whereas those produced by conscious patients can be volitional. Further investigation, however, reveals that reflexes cannot be reliably distinguished from conscious behaviors on the basis of any generalizable empirical characteristics. Ambiguity between reflexive and conscious behaviors undermines the capacity of the reflex to distinguish between disorders of consciousness and has implications for how these disorders should be conceptualized in future diagnostic criteria.

Bacteriological Profile and Sensitivity to Antibiotics of Common Isolates Responsible for Urinary Tract Infection in Nephrotic Children

Background: Prevalence of UTI in nephrotic children is high. It precipitates relapse and delays remission. The study was conducted to evaluate the prevalence of UTI, causative organisms and antibiotic sensitivity pattern in nephrotic children. Methods: This prospective study was carried out in a tertiary care Government Medical College of Eastern India for a time period of 1y among the admitted cases of nephrotic children between the age group of 2y to 12y. Urine specimens were routinely obtained by clean catch method following careful preparation of urethral orifices. The specimens were inoculated immediately on MacConkey’s agar and blood agar plates. Identification of the organisms and antibiotic susceptibility testing was performed according to CLSI guidelines 2010 by Kirby-Bauer disc diffusion method. Results: Total 111 nephrotic children were enrolled. Incidence of UTI was fairly high (27%) in nephrotic syndrome. E.coli (46%) was the most common organism responsible for UTI. Overall meropenem was the most sensititive perenteral drug (83%) for all isolates followed by amikacin (66%). Levofloxacin was the most common oral sensitive drug (75%). Conclusion: Common isolates of UTI in nephrotic children have developed resistance to commonly used oral or perenteral drugs. Empirically oral levofloxacin or perenteral amikacin should be started in nephrotic children with suspected UTI when culture report is pending to prevent full blown relapse and early response of proteinuria. Meropenem may be kept as reserve drug.

Age and prediction of remission and relapse of proteinuria and corticosteroid-related adverse events in adult-onset minimal-change disease: a retrospective cohort study

In adult-onset minimal-change disease (MCD) the predictors of remission and relapse of proteinuria and corticosteroid-related adverse events remain unknown. The multicenter retrospective cohort study, the STudy of Outcomes and Practice patterns of Minimal-Change Disease (STOP-MCD), included 142 adult-onset MCD patients in 5 nephrology centers in Japan. Primary outcomes were first remission of proteinuria defined by urinary protein (UP) <0.3g/day, UP/creatinine ratio (UPCR) <0.3, and/or negative/trace by dipstick test and first relapse of proteinuria defined by UP ≥1.0g/day, UPCR ≥1.0, and/or dipstick test ≥1+ followed by immunosuppressive therapy. Secondary outcomes were corticosteroid-related adverse events. During the median 3.6 (interquartile range, 2.0-6.9) years of the entire observational period, 136 (95.8%) and 79 (58.1%) patients developed at least 1 remission and 1 recurrence within a median of 15 (10-34) days and 0.90 (0.55-1.57) years, respectively. Compared with younger patients aged 15-29years at kidney biopsy, elderly patients aged ≥60years developed remission significantly later [hazard ratio 0.53 (95% confidence interval 0.32-0.88)], while older patients aged ≥45years were at a significantly lower risk of relapse [45-59years, 0.46 (0.22-0.96); 60-83years, 0.39 (0.21-0.74)]. However, older patients were significantly more vulnerable to severe infection, diabetes, and cataract as compared with younger patients. Younger patients had a higher risk of relapse while older patients had a lower risk of relapse but a higher risk of corticosteroid-related adverse events.

Rituximab Treatment for Membranous Nephropathy: A French Clinical and Serological Retrospective Study of 28 Patients

The development of well-tolerated and effective therapies that target the pathogenesis of membranous nephropathy (MN) would be useful. Our objective was to evaluate the efficacy of rituximab in MN. We analyzed the outcome of 28 patients treated with rituximab for idiopathic MN. Anti-PLA₂R antibodies in serum and PLA₂R antigen in kidney biopsy were assessed in 10 and 9 patients, respectively. Proteinuria was significantly decreased by 56, 62 and 87% at 3, 6 and 12 months, respectively. At 6 months, 2 patients achieved complete remission (CR) and 12 partial remission (PR; overall renal response, 50%). At 12 months (n = 23), CR was achieved in 6 patients and PR in 13 patients (overall renal response, 82.6%). Three patients suffered a relapse of nephrotic proteinuria 27–50 months after treatment. Univariate analysis suggested that the degree of renal failure (MDRD estimated glomerular filtration rate <45/ml/min/1.73 m²) is an independent factor that predicts lack of response to rituximab. Anti-PLA₂R antibodies were detected in the serum of 10 patients, and PLA₂R antigen in immune deposits in 8 of 9 patients. Antibodies became negative in all 5 responsive patients with available follow-up sera. In this retrospective study, a high rate of remission was achieved 12 months after treatment.

Circulating Anti-PLA2R Autoantibodies to Monitor Immunological Activity in Membranous Nephropathy

Experimental and human data converge to indicate that deposition along the glomerular basement membrane of immunoglobulins produced by autoreactive B cells may initiate a sequence of events resulting in complement activation,[1][1] impaired sieving function of the glomerular capillary wall and the

Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: a pilot clinical study

ObjectiveTo determine the safety and efficacy of allogeneic mesenchymal stem cell transplantation (MSCT) in refractory systemic lupus erythematosus (SLE).MethodsA total of 15 patients with persistently active SLE underwent MSCT. Outcome...

Predictors for progression in immunoglobulin A nephropathy with significant proteinuria

Proteinuria is a primary factor requiring treatment in immunoglobulin (Ig)A nephropathy. The purpose of this study was to assess the relevance of treatment response and relapse of proteinuria with renal function decline. One hundred and twenty-five biopsy-proven primary IgA nephropathy patients who had more than 1.0 g/day proteinuria at the first assessment were studied. All patients underwent anti-proteinuric treatment, and the association of the rate of renal function decline with treatment responsiveness, clinical and laboratory data was investigated. The treatment response of the patients was: 30.4% complete response (<0.3 g/day proteinuria), 32.8% partial response (0.3-1.0 g/day), 23.2% minimal response (decrement but not reduced to <1 g/day) and 13.6% no response (no decrement of proteinuria). The slope of renal function decline (-1.06 vs-1.24 mL/min per 1.73 m(2)/year, P = 0.580) was comparable between complete and partial response groups, but they were slower than those of minimal or non-response groups (P < 0.001). In multivariate analysis including other parameters, mean arterial pressure (MAP; beta = -0.240, P = 0.004) during follow up, minimal (beta = -0.393, P < 0.001) and non-response (beta = -0.403, P < 0.001) were significant predictors. In further investigation of complete and partial response groups, MAP (beta = -0.332, P = 0.001) and relapse of proteinuria (beta = -0.329, P = 0.001) were independently associated with slope of renal decline. Achievement of less than 1.0 g/day proteinuria and MAP were important for limiting the loss of renal function, and relapse of proteinuria should be closely monitored in proteinuric IgA nephropathy.

Neutrophil gelatinase-associated lipocalin (NGAL): a new marker of cyclosporine nephrotoxicity?

The aim of work was to investigate whether serum and urinary neutrophil gelatinase-associated lipocalin(sNGAL and uNGAL, respectively) are potential biomarkers of early cyclosporine A (CsA) nephrotoxicity in steroid-dependent nephrotic children (SDNS). The study group (I) consisted of 19 children with SDNS aged 9.46+/-5.52 years treated with CsA. The children were examined four times: at proteinuria relapse, prior to CsA treatment,then after 3, 6, and 12 months of CsA treatment. The control group (II) consisted of 18 healthy children aged 3-15 years. A commercial enzyme-linked immunosorbent assay method was used to measure NGAL concentration.The sNGAL level in SDNS children prior to the administration of CsA was similar to that in the healthy controls (p>0.05), but it increased significantly during the course of treatment (p<0.01). The uNGAL/creatinine (cr) ratio in SDNS patients was higher before the withdrawal of CsA therapy (p<0.05), and was also increased at the consecutive examinations (p<0.01). There was a positive correlation between both sNGAL and uNGAL levels and CsA serum level. However, based on the serum and urinary NGAL/cr receiver operating characteristic curve and area under the curve (AUC) analysis, it remains uncertain whether uNGAL is a good predictor of cyclosporine nephropathy. Both sNGAL and uNGAL concentrations increased during the course of CsA treatment. Further studies in larger groups of patients are therefore necessary to confirm our experimental data that increased NGAL levels may be a non-invasive marker for the early detection of tubulointerstitial damage in CsA nephrotoxicity.

Development of Focal Segmental Glomerulosclerosis after Anabolic Steroid Abuse

Anabolic steroid abuse adversely affects the endocrine system, blood lipids, and the liver, but renal injury has not been described. We identified an association of focal segmental glomerulosclerosis (FSGS) and proteinuria in a cohort of 10 bodybuilders (six white and four Hispanic; mean body mass index 34.7) after long-term abuse of anabolic steroids. The clinical presentation included proteinuria (mean 10.1 g/d; range 1.3 to 26.3 g/d) and renal insufficiency (mean serum creatinine 3.0 mg/dl; range 1.3 to 7.8 mg/dl); three (30%) patients presented with nephrotic syndrome. Renal biopsy revealed FSGS in nine patients, four of whom also had glomerulomegaly, and glomerulomegaly alone in one patient. Three biopsies revealed collapsing lesions of FSGS, four had perihilar lesions, and seven showed > or =40% tubular atrophy and interstitial fibrosis. Among eight patients with mean follow-up of 2.2 yr, one progressed to ESRD, the other seven received renin-angiotensin system blockade, and one also received corticosteroids. All seven patients discontinued anabolic steroids, leading to weight loss, stabilization or improvement in serum creatinine, and a reduction in proteinuria. One patient resumed anabolic steroid abuse and suffered relapse of proteinuria and renal insufficiency. We hypothesize that secondary FSGS results from a combination of postadaptive glomerular changes driven by increased lean body mass and potential direct nephrotoxic effects of anabolic steroids. Because of the expected rise in serum creatinine as a result of increased muscle mass in bodybuilders, this complication is likely underrecognized.

An unusual case of loin pain and nephritis

We report a 14-year-old girl with nephrotic syndrome and renal vein thrombosis (RVT) on initial presentation. The patient tested positive for antinuclear antibodies but only weakly positive for anti-double-stranded DNA (anti-dsDNA). Her C3 level was normal. Treatment with low molecular weight heparin resulted in resolution of RVT. Renal biopsy showed membranous glomerulonephritis with segmental sclerosis. Tissue immunostaining showed diffuse granular C3 and immunoglobulin (Ig)G staining along the capillary wall with focal segmental IgM staining deposits in the mesangium. No C1q, IgA, or fibrinogen was noted on immunofluorescence assay. With cyclosporin A and prednisolone, the patient went into remission and corticosteroids were tapered off gradually. Two years later, she had a relapse of proteinuria, hypocomplementemia, and extremely high anti-dsDNA. Systemic lupus erythematosus (SLE) was diagnosed, and she was promptly started on steroid and immunosuppressive agents, which resulted in reduction of proteinuria. Her renal function has been normal all along. Membranous nephropathy is uncommon in Chinese children and could be a possible early presentation of SLE.

Use of Rituximab in Focal Glomerulosclerosis Relapses After Renal Transplantation

Focal and segmental glomerulosclerosis (FSGS) accounts for more than 10% of all cases of renal diseases leading to renal failure in children. After renal transplantation, 20% to 40% of FSGS relapse, frequently leading to renal loss.Plasmapheresis is considered the first option to treat relapses by several authors but is often ineffective. The anti-CD20 monoclonal antibody rituximab has been proposed as a possible treatment. We reviewed the effect of rituximab in seven children or young adults with pretransplant FSGS and relapse of proteinuria after transplantation who did not respond to intensive plasmapheresis. After treatment, urine protein disappeared in three patients, was reduced by 70% in one patient and by 50% in one patient. No response was observed in one patient who had a quick deterioration of renal function and reached end-stage renal failure after 3 months. One additional patient developed a severe reaction a few minutes after the start of the first rituximab infusion. Rituximab is a possible option to treat some resistant cases of FSGS with relapsing proteinuria after transplantation. It is important that therapy is started early after evidence of failure of plasmapheresis, before sclerosis develops in the glomeruli. The response to treatment can occur after several months. During the follow-up period, CD19 cells should be monitored carefully, and additional rituximab infusions considered to maintain B-cell depletion.

Rituximab is an effective treatment for lupus nephritis and allows a reduction in maintenance steroids

Lupus nephritis is a life-threatening complication of SLE. Treatment regimes include steroids and cyclophosphamide, both associated with significant morbidity. Newer regimes include mycophenolate mofetil (MMF). We report our outcomes in a prospectively monitored cohort of patients receiving our new standard treatment protocol, comprising rituximab induction therapy and MMF maintenance in patients already taking maintenance immunosuppression for SLE who developed lupus nephritis. We then attempted steroid reduction/withdrawal. Patients with class III/IV/V lupus nephritis were included. All patients were on steroids prior to the development of lupus nephritis. Eighteen patients have reached at least 1 year follow-up. These patients received rituximab induction therapy and MMF maintenance therapy. Steroid reduction/withdrawal was guided by clinical response. Fourteen of 18 (78%) patients achieved complete or partial remission with a sustained response of 12/18 (67%) at 1 year, with 2 patients having a relapse of proteinuria. Four patients did not respond. There was a significant decrease in proteinuria from a mean protein:creatinine ratio (PCR) of 325 mg/mmol at presentation to 132 mg/mmol at 1 year (P = 0.004). Serum albumin significantly increased from a mean of 29 g/L at presentation to 34 g/L at 1 year (P = 0.001). The complication rate was low with no severe infections. Following treatment with rituximab, 6 patients stopped prednisolone, 6 patients reduced their maintenance dose and 6 patients remained on the same dose (maximum 10 mg). This data demonstrates the efficacy of a rituximab and MMF based regime in the treatment of lupus nephritis, allowing a reduction or total withdrawal of corticosteroids.

Successful Treatment of Membranous Glomerulonephritis with Rituximab in Calcineurin Inhibitor-Dependent Patients

Calcineurin inhibitors (CNIs) induce remission of proteinuria in most nephrotic patients with membranous glomerulonephropathy (MGN). However, 60% of patients become treatment dependent and are at risk of chronic nephrotoxicity. The aim of this study was to evaluate the efficacy of rituximab in patients with long-term dependence on CNIs. Thirteen patients with MGN, normal renal function, and proven dependence on CNIs, despite previous treatment with other immunosuppressant drugs, received a single trial of four weekly doses of rituximab (375 mg/m(2)). Outcome measures were the percentage of patients with CNI withdrawal and no evidence of relapse and the percentage of patients with complete or partial remission 30 mo after CNI withdrawal. After rituximab, proteinuria decreased significantly (2.5 +/- 0,76 basal versus 0.85 +/- 0.17 at 6 mo; P = .0003). CNIs and other immunosuppressant drugs could be withdrawn in all patients with no evidence of relapse. After CNI withdrawal, GFR increased significantly (90.3 +/- 15 basal to 106.4 +/- 20 at 3 mo with a mean increase of 15.3% [range 0-20]). Three patients suffered a relapse of nephrotic proteinuria 19, 23, and 28 mo after rituximab treatment; all were successfully treated with a second course of rituximab. At 30 mo, all patients were in remission. In patients with MGN with long-term CNI dependence, rituximab can be an effective tool to overcome dependence on CNI, thus avoiding the risk of nephrotoxicity related to the chronic exposure to these drugs.

Urinary levels of matrix metalloproteinases and their tissue inhibitors in nephrotic children

The aim of this study was to determine the effects of cyclosporine A (CyA) on urinary levels of matrix metalloproteinase 2 and 9 (MMP2, MMP9) and their tissue inhibitors 1 and 2 (TIMP1, TIMP2) in steroid-dependent nephrotic syndrome (SDNS). The study group (1) consisted of 18 children SDNS aged 3.5-17.0 years treated with CyA. All NS children were examined three times: (A) at proteinuria relapse, before CyA treatment, (B) after 6 months, and (C) after 12 months of CyA administration. The control group (2) consisted of 18 healthy children. Serum CyA level was assessed by immunofluorescence. Enzyme-linked immunosorbent assay kits for total human MMP2 and 9 and TIMP1 and 2 were obtained from R&D Systems. Compared with healthy controls, urinary MMP9/Cr in NS children before CyA was on the same level and increased during CyA treatment, and urinary TIMP1/Cr was twice as high and increased significantly during CyA treatment. MMP9/TIMP1 in NS children treated with CyA increased, but the difference was not statistically significant. Urinary MMP2/Cr was similar, and urinary TIMP2/Cr was significantly higher in children treated with CyA (p < 0.01). The MMP2/TIMP2 ratio in NS children treated with CyA was significantly lower in comparison with healthy controls (p < 0.01). A negative correlation was noted between urinary MMP2/TIMP2 ratio and serum CyA in NS children (r = -0.541, p < 0.01). An imbalance within the MMP2 and TIMP2 and MMP9 and TIMP1 system may play a role in the pathogenesis CyA nephropathy.

Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases

Several case reports suggest that rituximab (RTX) could be effective in steroid-dependent nephrotic syndrome, but RTX efficacy has not yet been studied in a series of patients. Safety and efficacy of RTX were assessed in a multicenter series of 22 patients aged 6.3-22 years with severe steroid-dependent nephrotic syndrome or steroid-resistant but cyclosporin-sensitive idiopathic nephrotic syndrome. Patients were treated with two to four infusions of RTX. Seven patients were nephrotic at the time of RTX treatment. Peripheral B cells were depleted in all subjects. Remission was induced in three of the seven proteinuric patients. One or more immunosuppressive (IS) treatments could be withdrawn in 19 patients (85%), with no relapse of proteinuria and without increasing other IS drugs. RTX was effective in all patients when administered during a proteinuria-free period in association with other IS agents. When relapses occurred, they were always associated with an increase in CD19 cell count. Adverse effects were observed in 45% of cases, but most of them were mild and transient. This study suggests that RTX could be an effective treatment for severe steroid-dependent nephrotic syndrome.

Stem cell mobilization in idiopathic steroid-sensitive nephrotic syndrome

Steroid-sensitive nephrotic syndrome (SSNS) is classically thought to be a T-cell disorder. The aim of this study was to examine whether or not thymus homeostasis was affected in SSNS. Mature and naive T cell recent thymic emigrants were quantified in the peripheral blood of nephrotic patients and controls. Because the generation of new T cells by the thymus ultimately depends on hematopoietic stem cells, CD34+ cells were also included in the study. Nineteen patients with SSNS during relapse, 13 with SSNS during proteinuria remission, and 18 controls were studied. Cell-surface markers (CD3, CD4, CD8, CD19, CD16, CD56, CD45RA, CD62L, CD34, and CD38) were analyzed by flow cytometric analysis. T-cell rearrangement excision circles (TRECs) were quantified in CD2+ cells by real-time polymerase chain reaction. Stroma cell-derived factor-1 (SDF-1) genotype and metalloproteinase-9 (MMP-9) plasma levels were also determined. Mature T cells (CD4+ and CD8+), circulating naive T cells (CD62L+ and CD3+ CD62L+), and recent thymic emigrants (CD45RA+) as well as TRECs, that measure thymus production, had a similar level in the three groups of patients. Conversely, CD34+ hematopoietic stem cells displayed a two-fold increase in SSNS patients during relapse either compared with controls or SSNS patients at remission. In addition, compared with controls, SSNS patients at remission displayed (1) a decrease in CD19+ cells (B cells) and (2) an increase in CD16CD56+ cells [natural killer (NK) cells]. In conclusion, thymus homeostasis is not significantly affected in nephrotic patients. Hematopoietic stem-cell mobilization at proteinuria relapse, as well as changes in B and NK cells during remission, suggest that SSNS might be due to a general disturbance of hematopoietic and immune cell trafficking.

Long-term follow-up of patients with IgA nephropathy treated with prednisolone and cyclophosphamide therapy

Analyses of selected cases suggest that immunosuppressive treatment could reduce proteinuria and delay the progression of immunoglobulin A nephropathy (IgAN). The aim of this study was to examine the long-term effectiveness of this therapy on the clinical course of IgAN. We also examined the relationship between the efficacy of the treatment and the suppression of the serum immunoglobulin level. Eighteen patients who were observed for more than 2 years after prednisolone and cyclophosphamide therapy were enrolled in this study. Their clinical and laboratory characteristics were recorded for 2-18 years (mean 7.8 +/- 5.7 years). Of the 18 patients, 13 had remission of proteinuria. We observed the subsequent development of proteinuria in four patients. Fourteen patients had remission of hematuria, with five patients experiencing subsequent relapse of hematuria. The mean time from the treatment to the relapse of proteinuria or hematuria was 5.8 years. Serum immunoglobulins were suppressed by the combination therapy. Serum IgG and IgM recovered 6 months after the treatment, whilst the suppression of serum IgA lasted for 4 years. We found a positive correlation between the serum IgA level and the degree of proteinuria. This study indicates that long-term follow-up is essential in order to prove the long-term benefit of immunosuppressive therapy in patients with IgAN. Careful monitoring of the serum IgA level may be useful in the follow-up of patients with IgAN, especially when they are treated with immunosuppressive agents.

Successful steroid treatment in a patient with membranoproliferative glomerulonephritis associated with hepatitis C virus

Thirteen years ago, a 65-year-old woman was diagnosed to have chronic active hepatitis with hepatitis C virus. After starting interferon alpha administration, she noticed edema and hypoalbuminemia. Renal biopsy revealed mesangial proliferation with focal endocapillary proliferation, and double contour of the glomerular basement membrane due to mesangial interposition. Interferon alpha was discontinued, and proteinuria and edema gradually decreased. She was re-admitted due to a relapse of proteinuria 8 years later. Biopsy revealed moderate mesangial and endcapillary proliferation presenting a lobular pattern, in addition to the presence of hyaline thrombi. Granular staining of immunoglobulin M and of C3 in capillary walls were detected. Since cryoglobulinemia was positive, a final diagnosis of cryoglobulinemic membranoproliferative glomerulonephritis was made. Prednisolone was started with an initial dose of 20 mg/day. Proteinuria and hypoalbuminemia improved, and prednisolone was tapered to 5 mg/day 9 months after the 2nd renal biopsy. The hepatitis C virus-RNA titer fluctuated.

Recurrence of Nephrotic Proteinuria in Children With Focal Segmental Glomerulosclerosis After Renal Transplantation Treated With Plasmapheresis and Immunoadsorption: Case Reports

Idiopathic focal segmental glomerulosclerosis (FSGS) is believed to be caused by a circulating permeability factor. FSGS recurrence is common after transplantation. The treatment is still a matter of debate; plasmapheresis (PE) and immunoadsorption (IA) are often used. We report on PE and IA in the treatment of two children with recurrent nephrotic proteinuria. Patient 1 was a 16-year-old girl who had recurrence of nephrotic proteinuria on the first day after transplantation (proteinuria-19 g/d). Primary immunosuppressive therapy was changed to high-dose cyclosporine and cyclophosphamide; plasmapheresis was started on day 4. Altogether we performed 53 PE and 38 IA procedures. During the first month, PE procedures were performed with no more than a 2-day interval between sessions, and the girl achieved partial remission (proteinuria 3 g/d). PE was then stopped. After 2 months, a relapse of heavy proteinuria occurred. This relapse was successfully treated again with intensified PE treatment. After achieving remission, a chronic PE regimen was started (PE once a week), similar to the previous series. The child remained in partial remission. Seven months after renal transplantation, she was switched from PE to IA, because of severe hypoproteinemia. Graft biopsy performed at 4 months showed effacement of the foot processes. At the present time she has a good graft function and 3 g/d proteinuria. Patient 2 was a 13-year-old girl with FSGS since 9 years. On the second day after renal transplantation she developed nephrotic proteinuria (proteinuria-14 g/d), which was treated with 39 PE and 16 IA treatments. She went into complete remission on the intensified PE regimen, had one relapse, and was switched to chronic IA. Graft biopsy performed at 2 weeks after transplantation showed effacement of the foot processes. At the present time she has good graft function and low proteinuria (0.3 g/d). In conclusion, intensified PE or IA treatments induced remission of recurrent nephrotic range proteinuria. Chronic PE or IA can maintain patients with frequent relapses in long-term remission.