Complete Remission Of Proteinuria Research Articles

Treatment of Hepatitis B Virus-Associated Membranous Nephropathy: Lamivudine Era versus Post-Lamivudine Era

Treatment of Hepatitis B Virus-Associated Membranous Nephropathy: Lamivudine Era versus Post-Lamivudine Era

Long‐term effect of rituximab in maintaining remission of recurrent and plasmapheresis‐dependent nephrotic syndrome post‐renal transplantation – Case report

Early recurrence of nephrotic syndrome after renal transplantation is a common serious adverse event in children with severe primary FSGS, affecting long-term outcome. There is no consensus in terms of uniform management in these cases. We describe the long-term effect of four unadjusted doses of 375 mg/m(2) i.v. rituximab, given to a five and a half-yr-old, nephrectomized child with immediate recurrence of nephrotic syndrome post-transplantation and dependency from repeated PF. Rituximab was introduced at three months post-transplantation after performing 18 sessions of PF and development of established dependency of the disease from plasma exchange. Complete remission of proteinuria was achieved with four doses, and it was maintained during next eight months of follow-up. Complete B CD(19) cell depletion was observed during four months after final dose, followed by severe depletion after eight months. No side effects of therapy were noted. Patient was free from PF, which was stopped while introducing rituximab, remaining non-proteinuric on triple immunosuppression (CsA, MMF, Pred).

A case of a 6-year-old girl with anti-neutrophil cytoplasmic autoantibody-negative pauci-immune crescentic glomerulonephritis

A 6-year-old girl was admitted to our hospital with proteinuria, hematuria, skin rash and joint pain of the lower limbs. Due to rapid progression of renal insufficiency, hemodialysis and peritoneal dialysis were performed. She was diagnosed with rapidly progressive glomerulonephritis. Kidney biopsy showed severe crescent formation (50% of glomeruli) and no deposition of any immunoglobulins or complements. Serologically, anti-neutrophil cytoplasmic autoantibody (ANCA) was negative not only by ELISA against proteinase-3 and myeloperoxidase-ANCA but also by indirect immunofluorescent assay against cytoplasmic and perinuclear ANCA. Anti-glomerular basement membrane antibody was also negative. In the acute phase, proinflammatory cytokines such as soluble tumor necrosis factor receptor 1 (sTNFR1), soluble interleukin (IL)-2 receptor (sIL2R), IL-6 and chemokine IL-8 were elevated. The patient was diagnosed with ANCA-negative pauci-immune crescentic glomerulonephritis (CrGN). Intensive treatment with methylprednisolone pulse therapy, plasma exchange, and multiple drug therapy including prednisolone and cyclophosphamide resulted in histopathological improvement and complete remission of proteinuria. There was a possibility that sTNFR1, sIL2R, IL-6 and IL-8 might be involved in the initiation and progression of ANCA-negative pauci-immune CrGN, and to remove and suppress these cytokines might be an effective way to treat ANCA-negative pauci-immune CrGN.

Remission of proteinuria and preservation of renal function in patients with renal AA amyloidosis secondary to rheumatoid arthritis

Renal AA amyloidosis presents as a life-threatening disease in patients with rheumatoid arthritis (RA). Although several newly developed immunosuppressive drugs have been tried, patients often progress to end-stage renal failure with unsatisfactory survival rate. A total of nine consecutive cases of severe nephrotic renal AA amyloidosis presented to us. Complete remission of proteinuria was observed in four cases (responders), and the remaining five reached the end point of haemodialysis or death (non-responders); these groups were retrospectively compared. The patients were treated with immunosuppressants, biological drugs and anti-hypertensive drugs. Levels of serum creatinine (S-Cr), urinary protein-creatinine ratio (UP/UCr), blood pressure (BP) and C-reactive protein (CRP) were measured. Histological characteristics of renal amyloid deposition and extent of kidney injury were also scored. Prior to treatment, clinical data (S-Cr, UP/UCr, BP and CRP) and histological severity (glomerular sclerosis, tubulointerstitial injury and extent of amyloid deposition) observed in the renal biopsy specimen were not significantly different between the groups. Following therapeutic intervention, proteinuria disappeared (UP/UCr <0.3) in responders within 12 ± 5.4 months but persisted in non-responders. Consequently, renal function stabilized in responders, but it deteriorated in all non-responders. Strict inflammatory control along with optimal control of hypertension was achieved in responders during the treatment. Regardless of histological severity, intensive therapeutic intervention that includes strict inflammatory control and optimal control of hypertension may change the histology-predicted prognosis of RA-associated renal AA amyloidosis.

Combination Treatment With Plasmapheresis and Rituximab for Recurrent Focal Segmental Glomerulosclerosis After Renal Transplantation

Therapy for recurrent focal segmental glomerulosclerosis (FSGS) in the renal allograft is largely based on case reports. The use of plasmapheresis alone (based on its effectiveness in children) appears less effective in adults, reaching a response rate of <40%. Recently, rituximab, an anti-CD20 monoclonal chimeric antibody, showed promising results as rescue therapy in plasmapheresis-resistant recurrent FSGS. However, following rituximab administration, response is variable, often slow and consequently overlooked. We report a series of four cases of recurrent FSGS following renal transplantation successfully treated with a combination of plasmapheresis and rituximab. Complete remission of proteinuria occurred in two and partial remission in the other two patients whereas renal function improved or remained stable. During treatment and the follow-up period (18-60 months) no severe infectious complications were observed. Our data suggest that the combination of plasmapheresis and rituximab is an acceptable treatment in patients with post-transplantation recurrent FSGS.

5 Complete Remission of Proteinuria with Cellcept and Cyclosporine in Non-HIV Collapsing Glomerulopathy

COMPLETE REMISSION OF PROTEINURIA WITH CELLCEPT AND CYCLOSPORINE IN NON-HIV COLLAPSING GLOMERULOPATHY Muhammad Rizwan Afzal; Antoine Samaha, Good Samaritan Hospital, Cincinna Ohio This case report is the first evidence of a successful treatment in a non-HIV pa ent with Collapsing Glomerulopathy (CG) using Cellcept and Cyclosporine. A 40-years old African American female presen ng with lower extremity edema was diagnosed with nephro c syndrome (Urine protein 10 gm/day, serum albumin 1.4 mg/dl, serum LDL 278 mg/dl & serum crea nine 2 mg/dl). A serological work up including ANA, An dsDNA, An SSA/SSB, An RNP, C-ANCA, P-ANCA, complement factors (C3, C4), HIV and hepa s panel was unremarkable. Renal ssue analysis with light microscopy, immunofluorescence and electron microscopy was consistent with collapsing variant of focal segmental glomerulosclerosis (FSGS). A steroid sparing immunosuppressive regimen consis ng of Cellcept (500 mg every 12 hours) and cyclosporine (3mg/kg/day) was started. Proteinuria started declining a er one month of treatment. The pa ent received cyclosporine for eight months and Cellcept for two years. Kidney func on remained stable during and six months a er discon nua on of treatment showing complete resolu on of proteinuria and hypoalbuminemia in recent lab work (Urine protein 0.3 gm/day, serum albumin 3.8 mg/dl & serum Crea nine 2.2 mg/dl). This case strongly suggests use of Cellcept and cyclosporine for treatment of CG variant of FSGS.

Nephrotic Syndrome and Idiopathic Membranous Nephropathy Associated with Autosomal-Dominant Polycystic Kidney Disease

We report the case of a 38-year-old male with autosomal-dominant polycystic kidney disease (ADPKD) and concomitant nephrotic syndrome secondary to membranous nephropathy (MN). A 3-month course of prednisone 60 mg daily and losartan 100 mg daily resulted in resistance. Treatment with chlorambucil 0.2 mg/kg daily, low-dose prednisone, plus an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin II receptor blocker (ARB) for 6 weeks resulted in partial remission of his nephrotic syndrome for a duration of 10 months. After relapse of the nephrotic syndrome, a 13-month course of mycophenolate mofetil (MFM) 2 g daily and low-dose prednisone produced complete remission for 44 months. After a new relapse, a second 24-month course of MFM and low-dose prednisone produced partial to complete remission of proteinuria with preservation of renal function. Thirty-six months after MFM withdrawal, complete remission of nephrotic-range proteinuria was maintained and renal function was preserved. This case supports the idea that renal biopsy is needed for ADPKD patients with nephrotic-range proteinuria in order to exclude coexisting glomerular disease and for appropriate treatment/prevention of renal function deterioration. To the best of our knowledge, this is the first reported case of nephrotic syndrome due to MN in a patient with ADPKD treated with MFM, with remission of proteinuria and preservation of renal function after more than 10 years. Findings in this patient also suggest that MFM might reduce cystic cell proliferation and fibrosis, preventing progressive renal scarring with preservation of renal function.

Cyclosporine A and steroid therapy in childhood steroid-resistant nephrotic syndrome

Background:In children, idiopathic nephrotic syndrome (INS) is primarily treated using corticosteroids. When remission is not achieved, the coadministration of potent immunosuppressant therapy becomes imperative. Cyclosporine A (CsA) is reportedly associated with a higher incidence of remission in comparison with other immunosuppressive agents.Methods:The present study investigated the response of combination therapy using CsA and prednisolone in 30 Tunisian children with idiopathic steroid-resistant nephrotic syndrome (ISRNS). Renal histopathology was compatible with focal segmental glomerular sclerosis (FSGS) in 15 children, minimal change disease (MCD) in nine children, and diffuses mesangiale proliferation (DMP) in six children.Results:The therapy protocol produced a complete remission of proteinuria in 15 patients (50%) and a partial remission in nine patients (30%). Six patients (20%) showed no response to therapy. Progression to end stage renal disease occurred in five CsA-resistant children and in four CsA-responsive patients. CsA-related nephrotoxicity was detected by renal biopsy in one patient.Conclusions:CsA remains the primary cytotoxic treatment for childhood steroid-resistant nephrotic syndrome. Its use in combination with corticosteroids provides optimum efficiency without high risk of nephrotoxicity.

Remission of refractory minimal change nephrotic syndrome after basiliximab therapy

Minimal change nephrotic syndrome has been proposed to be a disorder of T cell dysfunction. It is hypothesized that a circulating factor(s) from activated T cells might alter glomerular permeability to protein. Some studies have provided evidence that up-regulation of interleukin-2 may be involved, not only in the pathophysiology of minimal change nephrotic syndrome, but also in steroid resistance. Basiliximab, an anti-interleukin-2 receptor antibody, is indicated for the prophylaxis of acute organ rejection in adults and children with kidney transplants. Clinical trials have shown that basiliximab is effective and well tolerated. We describe here a pediatric patient who continuously had massive proteinuria and hypoalbuminemia for 5 years, despite pulse therapy with methylprednisolone and cyclophosphamide and prolonged oral treatment with cyclosporine and mizoribine. He had experienced several disease- and treatment-associated complications, such as bacterial infections, indirect inguinal hernias, and cataracts. After he had been given a single dose of basiliximab, he achieved complete remission of proteinuria and then discontinued all immunosuppressant treatment.

Rituximab and Chronic Plasmapheresis Therapy of Nephrotic Syndrome in Renal Transplantation Patients With Recurrent Focal Segmental Glomerulosclerosis

Focal segmental golmerulosclerosis (FSGS) recurs in 30% of patients with FSGS who received a first renal transplant and in more than 80% of patients receiving a second transplant after a recurrence. Plasmapheresis (PP) can reduce proteinuria and even induce complete remission of proteinuria. We studied the effects of rituximab therapy associated with chronic PP treatment of nephrotic syndrome among 3 adult renal transplant recipients with recurrent FSGS after a fourth, a second, or a third transplantation, respectively. All of these subjects had displayed recurrences in previous transplants. The 3 patients were treated with PP once a week after recurrence; the first and second patients were treated with PP before transplantation surgery seeking to prevent FSGS recurrence. The patients' follow-up times were 21, 35, and 33 months, respectively, before rituximab therapy. During that time, the patients were treated with 133, 62, and 94 PP sessions, respectively. All of the patients received rituximab (375 mg/m(2)/wk, 4 doses) and 1 PP session before each rituximab dose. We confirmed the effectiveness of rituximab therapy by demonstrating peripheral CD19 cells to be undetectable after therapy. None of the patients treated with rituximab achieved remission of proteinuria. One patient showed proteinuria reduced by 26%, the second by 44%, and the third had no change. None of the patients had infectious complications or graft loss at 1 month follow-up. Our experience with 3 adult renal transplant recipients with recurrent FSGS and chronic PP therapy showed failure of rituximab to achieve remission in nephrotic syndrome.

Glomerular Disease Associated with Takayasu Arteritis: 6 Cases Analysis and Review of the Literature

To evaluate the clinical features, renal histopathology and therapeutic response to glucocorticoid and immunosuppressive agents in patients with glomerular disease associated with Takayasu arteritis (TA). Patients with TA and renal biopsy-confirmed glomerular disease were investigated retrospectively. None of them had renal artery stenosis or occlusive changes. Six patients with glomerulopathy, accounting for 3.75% of the 160 TA patients admitted to our hospital at the same period, were analyzed. All of them were females with a mean age of 35.5 +/- 10.0 years. Four cases presented with lower extremity edema. Laboratory tests showed that one was nephrotic syndrome, three were nephrotic range proteinuria, and two of them had mild renal dysfunction. The other two patients were asymptomatic microscopic hematuria and proteinuria. Renal pathology revealed mild immunoglobulin A nephropathy in two cases, mild mesangial proliferative glomerulonephritis (GN), membranoproliferative GN, minimal change disease, and fibrillary GN in one case respectively. Five cases received glucocorticoids and cyclophosphamide therapy. Proteinuria and microscopic hematuria disappeared in 2 to 4 weeks after the initiation of therapy in three cases. The patient with membranoproliferative GN also reached complete remission of proteinuria and recovered renal function 6 months after the treatment. TA may induce glomerular disease as a part of its histological spectrum. Apart from ischemic glomerular disease, glomerular disease should be suspected when TA patients have microscopic hematuria or proteinuria, that may be therapeutically responsive to glucocorticoids and immunosuppressive agent in relative early phase.

Inhibition of tumour necrosis factor alpha in idiopathic membranous nephropathy: a pilot study

Tumour necrosis alpha has been implicated in the pathogenesis of autoimmune disorders was to evaluate the safety, tolerability and potential efficacy of the tumour necrosis factor alpha (TNF-alpha) inhibitor, etanercept (ET), in patients with idiopathic membranous nephropathy (MN). Patients with biopsy-proven MN, nephrotic-range proteinuria and clearance of creatinine 50 ml/min or more were included in the study. Exclusion criteria were treatment with steroids or cyclosporine during the previous 3 months, or cytotoxic agents within 6 months prior to entry. ET was administered subcutaneously, 25 mg twice per week for 3 months. Plasma levels of TNF-alpha, interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), soluble intercellular adhesion molecule type 1 (sICAM-1), E-selectin, and the soluble form of tumour necrosis factor receptor-55 (sTNFR-55) were measured on entry and at Months 3, 6, and 9 after commencing therapy. Twelve patients were entered in the study (four females/eight males, mean time from diagnosis 8.3 months). The therapy was well tolerated; no infections or other adverse events were recorded by the end of follow-up. Two patients exhibited complete remission of proteinuria for at least 4 years. No significant change was found in the levels of TNF-alpha, IL-1, IL-6, IL-8 and IL-10 during the study. Similarly the levels of E-selectin and sICAM-1 were not significantly altered by therapy. Although we found no change in sTNFR-55 at 3 and 6 months, the levels of sTNFR-55 were found significantly decreased 9 months after therapy (mean difference from baseline: 334 +/- 527 pg/ml, P = 0.028). Short-term use of ET in a small series of patients reduced sTNFR-55 levels but did not exhibit any significant clinical effect in the majority of patients.

Coeliac disease and membranous nephropathy

Celiac disease results from the interaction between gluten and immune, genetic, and environmental factors. Although the main clinical manifestations are derived from gastrointestinal system, it has been described some renal diseases, especially chronic glomerulonephritis. We describe a young female patient with celiac disease that it appears after delivery. Moreover, she develops simultaneously nephrotic proteinuria and microhematuria as a result of membranous nephropathy. The treatment with gluten-free diet and other conservative measures (ACEI and statin) is followed by clinical improvement and simultaneous decrease of tissue antitransglutaminase IgA-antibodies and complete remission of proteinuria. We review the relationship between celiac disease and membranous nephropathy and the role of diet in the management of both diseases.

Idiopathic collapsing glomerulopathy in children

Collapsing glomerulopathy (CG) is a clinically and pathologically distinct variant of focal segmental glomerulosclerosis (FSGS). Pathologically similar lesions have been reported in adults and children with human immuno-deficiency virus (HIV) infection. However, there is a recent interest in the recognition of this variant in the absence of HIV infection. To evaluate the clinical presentation and outcome of our pediatric patients with idiopathic CG. A sum of six children with idiopathic CG, aged 1-7 years at presentation, were retrospectively identified. Clinical data and renal biopsy were reviewed for all patients. Serum creatinine and estimated GFRs at presentation and last follow-up were compared using the Wilcoxon signed rank test and the risk factors for occurrence of ESRD analyzed using the Cox proportional hazard models. Steroid-resistant nephrotic syndrome with or without azotemia was the presenting clinical finding in all the cases. The median serum creatinine values at onset and last follow-up were 1.05 and 1.25 mg/dl, respectively (p = 0.128). Following immunosuppressive therapy one patient achieved complete remission of proteinuria, and four were in partial remission. The remaining one patient did not show any change in proteinuria at 6 months of therapy. Two of the six patients progressed to end-stage renal disease within a median follow-up period of 27 months (range 14-96 months). Collapsing glomerulopathy is an aggressive variant of focal segmental glomerulosclerosis. All patients with CG should be screened for the underlying etiology, and patients with idiopathic CG should be offered a trial of immunosuppressive therapy.

Cyclosporine in the treatment of membranoproliferative glomerulonephritis.

Therapeutic approach to patients with idiopathic membranoproliferative glomerulonephritis is still controversial. Because it is more common in developing countries, the studies about it are limited. We used cyclosporine to treat 18 patients with membranoproliferative glomerulonephritis who were resistant to other treatment protocols such as using aspirin, dipyridamole, or steroids. All patients were treated with cyclosporine plus low-dose prednisone and were followed for an average 108 weeks. Partial or complete remission of proteinuria occurred in 94% of the patients (P<0.01). Relapse occurred in one (14.2%) of remitters after discontinuation of the drug. But the remainder stayed in remission to the end of the observation period. There was a 507% decrease in the baseline creatinine clearance in one patient (5.5%). These results suggest that cyclosporine may be an effective therapeutic agent in the treatment of resistant idiopathic membranoproliferative glomerulonephritis. Although the response is appeared later than other types of glomerulonephritis, but a long-term decrease in proteinuria and preservation of filtration function were observed in a significant proportion of the treated patients.

Minimal change nephrotic syndrome after stem cell transplantation: a case report and literature review

Graft-versus-host disease is one of the most frequent complications occurring after haematopoietic stem cell transplantation. Recently, renal involvement has been described as a manifestation of chronic graft-versus-host disease. Immunosuppression seems to play a major role: clinical disease is triggered by its tapering and resolution is achieved with the resumption of the immunosuppressive therapy. Prognosis is apparently favourable, but long term follow up data are lacking.We report a case of a 53-year-old man who developed nephrotic syndrome 142 days after allogeneic stem cell transplantation for acute myeloid leukaemia. Onset of nephrotic syndrome occurred after reduction of immunosuppressants and was accompanied by manifestations of chronic graft-versus-host disease. Histological examination of the kidney was consistent with Minimal Change Disease. After treatment with prednisolone and mycophenolate mofetil he had complete remission of proteinuria and improvement of graft-versus-host disease. Eighteen months after transplantation the patient keeps haematological remission and normal renal function, without proteinuria.Since patients with chronic graft-versus-host disease might be considered at risk for development of nephrotic syndrome, careful monitoring of renal parameters, namely proteinuria, is advisable.

Renin-angiotensin axis blockade reduces proteinuria in presymptomatic patients with familial FSGS

Familial and genetic forms of focal segmental glomerulosclerosis (FSGS) are associated with six different mutations in genes affecting the podocyte (NPHS2, ACTN4, CD2AP, WT1, TRPC6, and PLCE1). Immunosuppressive agents are often unsuccessful in treating this condition. Data regarding the efficacy of renoprotection through blockage of the renin-angiotensin axis is lacking. We describe three children from two different families with familial FSGS in whom partial to complete remission of proteinuria was attained through early blockade of the renin-angiotensin axis. In addition, there was no deterioration of renal function. We speculate that presymptomatic patients with normal renal function who have genetic or familial FSGS may benefit from early blockade of the renin-angiotensin axis and that this may also prevent progressive renal disease.

KIDNEY FAILURE STABILIZES AFTER AN INCREASE OVER 2 DECADES

The level of proteinuria is one of the most important predictors for progressive renal function loss in kidney disease. Reduction of urinary protein levels by renin-angiotensin-system (RAS) inhibitors limits renal function decline in patients with non-diabetic and diabetic nephropathies to the point that remission of the disease and regression of renal lesions have been reported. The increasing use of these drugs is possibly at the basis of the stabilization of rates of new cases of kidney failure reported to the US Renal Data System after a 2-decade period of progressive increases. RAS inhibition, however, may not be effective to the same degree in all patients. For those patients who do not reach a complete remission of proteinuria, treatment procedures to implement renoprotection should include strict blood pressure control (and metabolic control in diabetics), lowering of blood lipids, and lifestyle modifications. Early intervention may be important to maximize renoprotection, especially in diabetics.

Does remission of renal disease associated with antihypertensive treatment exist?

In diabetic and nondiabetic chronic nephropathies, high blood pressure and urinary loss of proteins represent major determinants of progressive renal function decline. Reducing blood pressure with drugs that inhibit the renin-angiotensin system also lowers glomerular hypertension and ameliorates glomerular sieving properties, thus reducing proteinuria. Reducing urinary protein levels with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor antagonists (ARA) limits renal function decline to the point that remission of disease and regression of renal lesions have been observed in experimental animals and in humans. This therapy, however, may not be effective in all patients. For patients who do not achieve complete remission of proteinuria, renoprotective treatment should include intensified blood pressure control (and metabolic control in diabetes) and amelioration of dyslipidemia. Early intervention, before progressive glomerulosclerosis and scarring is initiated by increased protein traffic, may be important to maximize reno- and cardioprotection, especially in diabetes.

Rapamycin-associated post-transplantation glomerulonephritis and its remission after reintroduction of calcineurin-inhibitor therapy

Abstract Rapamycin is a new immunosuppressive agent approved for maintenance therapy after kidney transplantation. It may allow calcineurin-inhibitor-free, nonnephrotoxic immunosuppression. We report, however, on four kidneytransplant recipients who developed post-transplantation glomerulonephritis after conversion from a calcineurin-inhibitor-based immunosuppression to rapamycin. In all four patients nephrotic-range proteinuria occurred 2–9 months after conversion to rapamycin. Renal biopsy confirmed membrano-proliferative glomerulonephritis type 1 in one case, membranous glomerulonephritis in another and IgA-nephropathy in two cases, respectively. Calcineurin-inhibitorbased immunosuppression was reintroduced and resulted in complete remission of proteinuria and in stabilised renal function in all patients. We conclude that in the case of rapamycin-associated post-transplantation glomerulonephritis an attempt should be made to replace rapamycin by a calcineurin inhibitor.