Recurrence Of Nephrotic Syndrome Research Articles

Successful steroid pulse treatment in childhood acquired haemophilia with nephrotic syndrome

We encountered a 2-year-old boy with acquired haemophilia, which rarely occurs in children, who was complicated with nephrotic syndrome. In mid-August 2001, he was diagnosed to have nephrotic syndrome based on the presence of massive proteinuria and hypoalbuminaemia. Activated partial thromboplastin time (APTT) was normal at 42.4 s at that time. After starting prednisone administration of 2 mg kg(-1) day(-1), the proteinuria disappeared immediately. However, in early October the same year, subcutaneous ecchymosis and intramuscular bleeding occurred for no apparent reason, and from the examination results his APTT was 106.4 s, factor VIII (FVIII) activity was <1%, and the anti-FVIII inhibitor titre was 6.9 BU ml(-1). As a result, he was diagnosed to have acquired haemophilia. The anti-nuclear antibody and anti-phospholipid antibody were negative. With recombinant activated FVII, haemostasis was obtained, and after administering three courses of steroid pulse therapy (methyl prednisolone: 20 mg kg(-1) day(-1) x 3 days), the anti-FVIII inhibitory activity disappeared. An analysis of the immunological and coagulation properties of his FVIII autoantibodies showed the anti-FVIII inhibitory activity to be mediated by IgG(1) antibody. In other words, his FVIII inhibitor was a Th1 dominant and it provided a good response to treatment. These findings correlate with those of previous reports. The patient thereafter frequently demonstrated a recurrence of nephrotic syndrome. As a result, he is presently being managed with cyclosporine. However, no recurrence of the anti-FVIII titre has been observed.

Hypocitraturia as a risk factor for nephrocalcinosis after kidney transplantation

Calcium-oxalate crystal deposition in kidney transplant biopsy specimen led us to investigate the impact of calcineurin inhibitor treatment on urinary excretion of lithogenic and stone inhibitory substances in 53 children after successful kidney transplantation (KTx) receiving cyclosporine A (CsA) or tacrolimus. We compared the values obtained with those of 12 patients with recurrent nephrotic syndrome under CsA and of 6 patients with Rasmussen encephalitis (RE) under tacrolimus therapy. Renal ultrasound examinations were repeatedly performed. Hypocitraturia was found in 69% of patients, with KTx patients having a significantly lower urinary citrate excretion than those receiving calcineurin inhibitors for other reasons. Secondly, we found hyperoxaluria in 35% of patients, again especially in those after KTx. No significant difference in urinary substances was seen comparing CsA with tacrolimus treatment. Urolithiasis was found in one and calcium-oxalate crystal deposition in biopsy specimen of three KTx patients. Calcineurin inhibitor treatment can lead to significant hypocitraturia, especially in patients after KTx receiving the highest dose of medication. Hyperoxaluria is primarily the result of a removal of significant body oxalate stores, deposited during dialysis, but may not be suspected as a specific side effect of calcineurin inhibitor therapy. Both findings can increase the risk for urolithiasis or nephrocalcinosis.

Evolution of nephrotic-associated focal segmental glomerulosclerosis and relation to the glomerular tip lesio

Several entities or variants within focal segmental glomerulosclerosis (FSGS) have been described, but their changes with time and interrelationships are undetermined. Changes with time were studied in two series of segmental sclerosing lesions in the nephrotic syndrome, one of 22 specimens from ten patients in a trial, the other of 176 specimens from 121 consecutive patients. The earliest lesions were probably all at the tubular origin, equivalent to the tip variant of FSGS. In some patients, lesions remained at this site, but progression to renal failure was accompanied by morphologic progression, with development of lesions at various sites, equivalent to FSGS, not otherwise specified (NOS). Progression was more likely if there were large lesions, abnormal mesangium, and extensive acute tubular damage. Patients with lesions at the tubular origin at presentation had a shorter duration of symptoms and less chronic renal damage than those with multiple lesions, were more likely to have a complete response of the nephrotic syndrome, and were less likely to progress to renal failure. Recurrent nephrotic syndrome occurred in 12 of 14 allografts at risk, and was usually accompanied by lesions at the tubular origin, then multiple lesions. At least some patients with FSGS (NOS) have evolved from the tip variant. The tip variant has been considered a distinct entity. Another interpretation is that it includes two conditions, one an early form of classic FSGS, and the other closely related to minimal change nephropathy (MCN), equivalent to the glomerular tip lesion as originally defined.

The Effect of Urinary Protein Excretion in Post–Renal Transplant Recurrent Nephrotic Syndrome on Basiliximab Pharmacokinetics and Pharmacodynamics in a Pediatric Patient

A pharmacokinetic and pharmacodynamic study of Basiliximab therapy has not been reported in recurrent post–renal transplant nephrotic syndrome. We assessed the effect of urinary protein in a focal segmental glomeruloscrelosis patient. We measured the serum concentrations of basiliximab as well as the rate of activated CD25-positive T lymphocytes at fixed intervals in nephrotic versus eight nonnephrotic pediatric post–renal transplant patients. A significant reduction in the antibody concentrations was observed in focal segmental glomeruloscrelosis. The CD25 expression rate showed a similar trend to the pharmacokinetic data. We conclude that cases of massive urinary protein excretion need special care to maintain immunosuppression in renal transplant using Basiliximab.

Genetic forms of nephrotic syndrome

Mutations of NPHS1, NPHS2, or WT1 may be responsible for severe forms of nephrotic syndrome in children, progressing to end-stage renal failure. Recent studies have shown that congenital nephrotic syndrome may be secondary to mutations of one of these three genes and that some patients have a digenic inheritance of NPHS1 and NPHS2 mutations. The clinical spectrum of NPHS2 mutations has broadened, with the demonstration that mutations in the respective gene podocin may be responsible for nephrotic syndrome occurring at birth, in childhood, or in adulthood. It is now well recognized that podocin mutations are found in 10%-30% of sporadic cases of steroid-resistant nephrotic syndrome with focal segmental glomerulosclerosis. Data from large cohorts indicate that the risk of recurrence of nephrotic syndrome after renal transplantation in patients with podocin mutations is very low.

The pediatric nephrotic syndrome spectrum: clinical homogeneity and molecular heterogeneity.

Idiopathic nephrotic syndrome is the most common glomerular disorder of childhood. Recurrence of nephrotic syndrome immediately following renal transplantation is rapid, results in a high rate of graft loss, and represents the most severe form of nephrotic syndrome. This review discusses the molecular heterogeneity of pediatric nephrotic syndrome across the spectrum of disease activity. A schema is offered for a molecular approach to pediatric nephrotic syndrome, including immune-mediated and structural/genetic factors.

High-dose oral cyclosporin therapy for recurrent focal segmental glomerulosclerosis in children

Background:Focal segmental glomerular sclerosis (FSGS) has a high propensity for recurrence after renal transplantation, with a 50% risk for graft failure from recurrent disease. Methods:We report on the efficacy of high-dose oral cyclosporin A (CsA) in the treatment of recurrent FSGS in children. Between August 1991 and January 2003, a total of 24 patients with FSGS underwent transplantation at 1 institution. Sixteen patients (67%) had recurrent disease. In these 16 patients, CsA dose was increased gradually until remission was achieved or there was evidence of renal toxicity. Seven patients also underwent plasma exchange. Results:Thirteen patients (81%) achieved remission. Remission was complete in 11 patients and partial in 2 patients. The CsA dose necessary for inducing remission ranged from 6 to 25 mg/kg/d. Four of these patients also underwent plasma exchange. After remission, CsA dose was reduced gradually toward the standard posttransplantation regimen. Eleven of 13 responders have a functioning graft after a follow-up ranging from 10 months to 12 years. One graft was lost because of recurrent FSGS, and another graft because of recurrence and cellular rejection; noncompliance was a factor in both losses. The 3 patients with disease that did not respond to high-dose CsA therapy lost their grafts because of recurrent FSGS. A common factor in these 3 patients was the inability to increase the CsA dose because of early evidence of nephrotoxicity, evidenced by an increase in serum creatinine level. Conclusion:High-dose oral CsA therapy is effective in producing long-lasting remission of recurrent nephrotic syndrome in children with FSGS.

Recent advances in congenital nephrotic syndrome.

This review provides a concise update of the most recent literature related to the diagnosis and care of patients with congenital nephrotic syndrome. This topic is of particular interest in light of the rapidly growing body of literature regarding mutations of proteins such as nephrin and podocin that are expressed at or near the podocyte slit diaphragm. The phenotypic variance of patients with congenital nephrotic syndrome with nephrin and podocin mutations resulting from triallelic mutations represents an important advance in our understanding of the effect of multiple genetic mutations on clinical disease expression. Clinically, the management of patients with unilateral nephrectomy, rather than the classic bilateral nephrectomy, represents an efficacious alternative management strategy and may impart better chances of graft survival by allowing later transplantation. Identification of a subset of patients with congenital nephrotic syndrome at increased risk of recurrence who also have antinephrin antibodies may enhance our understanding of recurrent disease in congenital nephrotic syndrome after transplantation. Exciting recent findings in the genotypic/phenotypic correlations of patients with congenital nephrotic syndrome may not only modify our understanding of this disease but may also help to revolutionize our understanding of human genetics. Promising outcomes with unilateral nephrectomy in patients with congenital nephrotic syndrome have permitted transplantation to be delayed and may potentially decrease the risk of complications. New findings regarding recurrence of nephrotic syndrome in patients with congenital nephrotic syndrome after transplantation may lead to improved survival in future renal transplantations.

Recurrent minimal change disease post-allograft renal transplant

A young adult was diagnosed with steroid-resistant minimal change disease (MCD) without evidence of focal segmental glomerulosclerosis (FSGS) despite serial and detailed sectioning and screening of the renal biopsy. He received initial treatment with steroids and then cyclosporine plus low-dose steroids for 2 years. Renal function progressively deteriorated due to resistance to steroid and cyclosporine. Two months after initiation of hemodialysis, the patient received a living-related allogenic kidney transplant. However, recurrent nephrotic syndrome and renal insufficiency occurred after transplantation. In spite of aggressive treatment, renal function showed no significant improvement. The kidney graft was removed 2 weeks after transplantation. Serial sectioning and thorough sampling and screening revealed no evidence of FSGS, but light microscopy and electron microscopy showed the typical morphologic pattern of MCD, corresponding to the pretransplant diagnosis. We believe that this is the first reported case of recurrent MCD after renal transplant.

Recurrent Nephrotic Syndrome Induced by Nonsteroidal Anti-inflammatory Drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are well known potential nephrotoxic agents with a wide range of different effects on the kidney. One less commonly seen effect is nephrotic syndrome. The following case demonstrates the easily overlooked possibility of NSAIDs being a cause of nephrotic syndrome. [ Hong Kong J Nephrology 2003;5(2):98-100]

Clinical study on effect of shenbing mixture in reducing recurrence of simple nephrotic syndrome of children

To observe the effect of Shenbing Mixture (SBM) of the recurrence of simple nephrotic syndrome of children. Sixty-eight patients treated with SBM combined with prednisone were observed and compared with those in the control group treated with prednisone alone. The 1-year recurrence rate of the treated group was 14. 3% , which was obviously lower than that in the control group (59.3%,P<0. 01). Serum level of Cortisol, IgG, IgA, CD3, CD4, CD4/ CD8 ratio and rosette formation rate of RBC-C3b in patients before treatment were all significantly lower than normal range. After being treated with SBM combined with prednisone, the above-mentioned indexes were all improved significantly and close to normal. SBM had obvious effect in reducing recurrence of nephrotic syndrome in children, the mechanism is closely related to multiple pathways, including adjustment of T-lym-phocyte dysfunction, improving humoral immunity and RBC immune function, and promoting the recovery of adrenal cortex function.

Treatment of primary focal segmental glomerulosclerosis

Urinalysis had 4 protein with 5 red blood cells/high-power field along with granular and waxy casts. A 24-hour urine collection contained 8.2 g of protein, and the creatinine clearance was 42 mL/min. The sedimentation rate was 64 mm/h; rheumatoid factor and ANA were normal; C3, 135 mg/dL; C4, 41 mg/dL; and both urine and serum immunoelectrophoresis were negative for paraproteins. A rapid plasma reagin test (RPR) was nonreactive. Hepatitis B surface antigen was negative as was an ELISA evaluation for HIV antibody. A chest radiograph demonstrated her heart to be normal in size, and her lungs were clear, but bilateral pleural effusions were noted. An ultrasound of the kidneys demonstrated them to be normal in size and echogenicity. The renal arteries and veins were patent. A sodiumand water-restricted diet was prescribed, and the patient was treated with furosemide with good response. She underwent a percutaneous renal biopsy 3 weeks after presenCASE PRESENTATION tation. At the time of the biopsy, her blood urea nitrogen was A 53-year-old African American woman who had previously 29 mg/dL; serum creatinine, 3.2 mg/dL; serum albumin, 1.1 been in excellent health presented 11 years ago with increasing g/dL; and cholesterol, 784 mg/dL. weight, leg edema, and facial swelling that had developed over The renal biopsy revealed 17 glomeruli by light microscopy; one month. She had no history of sickle cell disease, recurrent one was hyalinized. The remaining glomeruli manifested mildly urinary tract infections or pyelonephritis, vesicoureteral reflux, increased mesangial matrix and cellularity. The glomerular basediabetes mellitus, hypertension, renal or systemic diseases, or ment membranes were thin and delicate, and the capillary loops morbid obesity. There was no family history of hypertension were patent. One glomerulus had a segmental scar with hyalinoor renal disease. She had not been taking any prescribed medisis, and a second glomerulus had a segmental scar with a small cations nor had she been using nonsteroidal anti-inflammaadhesion to Bowman’s capsule. Acute tubular necrosis and intertory agents. stitial edema were evident but no significant tubulointerstitial Physical examination revealed: blood pressure, 120/84 mm Hg; atrophy or fibrosis was seen. Immunofluorescence examination no skin rashes; lungs were clear; cardiac examination was norof the tissue was negative. Electron microscopy disclosed difmal; no hepatosplenomegaly; and no significant lymphadenopfuse foot process fusion with villous transformation; no elecathy. Her joints were unremarkable but she had 3 pre-tibial tron-dense deposits were seen in the mesangium or along the edema bilaterally. Laboratory evaluation demonstrated a blood capillary wall. urea nitrogen of 32 mg/dL; serum creatinine, 1.8 mg/dL; albuThe patient was given oral prednisone, 60 mg/day; 2 weeks min, 1.6 g/dL; and cholesterol, 612 mg/dL. Hemoglobin was 14.6 later her serum creatinine had fallen to 0.9 mg/dL but the proteing/dL with a normal white blood cell count and platelet count. uria had risen to 12.4 g/day. However, after 2 months of highdose steroid therapy, the proteinuria had decreased to 0.1 g/day, the serum albumin level was 3.8 g/dL, and the cholesterol level Portions of this article are republished with permission from Korbet was down to 326 mg/dL; she was edema free. A steroid taper SM: Primary focal segmental glomerulosclerosis, in Therapy in Nephrolwas completed over an additional 2 months. One week after ogy and Hypertension: A Companion to Brenner and Rector’s The Kidney (2nd ed), edited by Brady RJ, Wilcox CS, Philadelphia, W.B. Saunders discontinuing steroids she had a relapse of the nephrotic syn(in press). drome (13.6 g/day) but again responded to a second course of high-dose prednisone with a complete remission. She remained The Nephrology Forum is funded in part by grants from Amgen, in a complete remission for 4 months after the discontinuation Incorporated; Merck & Co., Incorporated; Dialysis Clinic, Incorpoof steroids and then relapsed a second time (proteinuria of 13 rated; and Bristol-Myers Squibb Company. g/day). She was treated with prednisone and oral cyclophospha

A case of recurrent parotid swelling, syncope, arthritis and nephrotic syndrome

AbstractThe differential diagnoses and histopathological findings of a case of recurrent parotid swelling, syncope, arthritis and nephrotic syndrome will be discussed. Primary Sjögren's syndrome is rarely associated with granulomatous inflammation, panniculitis and systemic amyloidosis. Multi‐organ failure, in particular cardiac amyloidosis, is potentially fatal.

Elevation of urinary IL-1β levels during transplant associated nephropathy in rat model of the nephrotic syndrome

A recurrence of nephrotic syndrome is a well-known phenomenon in patients who receive kidney transplantation. In this study, we attempt to establish a rat model of recurrent nephrotic change after renal transplantation using puromycin aminonucleoside (PA) induced nephrotic rats. We then examine the mechanism leading to recurrence. Female Sprague-Dawley rats (8 weeks) were divided into four groups: group A, allogenic renal transplantation of a normal kidney to PA-induced nephrotic rats; group B, PA injection only as a nephrotic control; group C, allogenic transplantation of a normal kidney to rats receiving a saline injection; group D, rats receiving only a saline injection. The serum and urinary levels of protein, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-2 and interferon (IFN)-gamma were measured. The cytokine levels were assessed by performing enzyme-linked immunosorbent assays. Six days after renal transplantation, the kidneys were excised, tissue sections were stained with hematoxylin-eosin and the specimens were studied for pathological alterations. The urinary protein levels and the histological results of protein casts in renal tubules of the autologous kidneys of the nephrotic rats and the transplanted kidneys confirmed the recurrence of nephrotic syndrome in the transplanted kidney. After renal transplantation, urinary protein and IL-1beta levels were significantly elevated in recurrent transplanted kidney groups compared with those in the control groups, while the TNF-alpha, IL-2, and IFN-gamma levels were not elevated. In addition, serum levels of TNFalpha and IL-1beta were not elevated. These results suggested that IL-1beta may relate to the recurrent nephropathy in the transplanted kidney in the nephrotic rat.

Recurrence of nephrotic syndrome in kidney grafts of patients with congenital nephrotic syndrome of the Finnish type: role of nephrin.

Congenital nephrotic syndrome of the Finnish type (CNF, NPHS1) is caused by mutations in the NPHS1 gene. NPHS1 codes for nephrin, a cell adhesion protein located at the glomerular slit diaphragm. Renal transplantation is the only treatment option for most patients with NPHS1. We have previously described recurrence of severe proteinuria in grafts transplanted to children with NPHS1. Here we studied the pathophysiology of this proteinuria. Clinical data, light and electron microscopic findings as well as the expression of nephrin in the proteinuric grafts were studied. The patients' sera were screened for antibodies against kidney glomerulus and nephrin molecule using indirect immunofluorescence and ELISA. Fifteen episodes of recurrent nephrotic syndrome occurred in 13 (25%) of 51 grafts transplanted to 45 Finnish children with NPHS1. All nine patients with recurrence had a Fin-major/Fin-major genotype, which leads to absence of nephrin in the native kidney. Rescue therapy (cyclophosphamide) was successful in seven episodes, but six kidneys were lost due to this process. Antibodies reacting against glomerulus were found in eight, and high anti-nephrin antibody levels were detected in four of the nine patients. In electron microscopy, the fusion of the foot process and decreases in the detectable slit diaphragms in the podocyte pores were observed. The expression of nephrin mRNA was markedly reduced in two, and granular staining for nephrin was seen in three of five grafts. Circulating anti-nephrin antibodies seem to have a pathogenic role in the development of heavy proteinuria in kidney grafts of NPHS1 patients with Fin-major/Fin-major genotype.

Single-center analysis of early recurrence of nephrotic syndrome following renal transplantation in children.

Recurrence of nephrotic syndrome (NS) after transplantation (Tx) occurs in 20-50% of renal transplant recipients, with a median time to recurrence of 14 days and a 50% rate of graft loss. We performed a retrospective analysis of 22 pediatric patients with NS who received renal transplants at the Children's Hospital, Boston, between 1982 and 1999. During the first 14 days following Tx, 13 (59%) patients developed clinical recurrent nephrotic syndrome (RNS). RNS developed in 50% of living donor recipients and in 70% of cadaveric donor recipients (p= non-significant). Seven of the 13 patients with RNS were treated with plasmapheresis, while six received standard immunosuppressive induction therapy only. Two of the seven treated patients and one of the six untreated patients lost their grafts to RNS, yielding a total RNS graft loss rate of 23%. However, patients with RNS who achieved remission had significantly higher cumulative graft survival at 5 yr than did RNS patients who did not achieve remission (p< 0.001). Overall cumulative graft survival at 5 yr was not significantly different between the two groups: 67% in those with non-recurrent nephrotic syndrome (NRNS) vs. 64% in those with RNS, p= non-significant. We conclude that successful reversal of early RNS improves long-term graft survival in pediatric RNS. Multi-center studies are sorely needed to develop novel, less toxic therapies for native and recurrent NS.

Tryptophan immunoadsorption strongly reduces proteinuria in recurrent nephrotic syndrome

Tryptophan immunoadsorption strongly reduces proteinuria in recurrent nephrotic syndrome

New Aspects of the Treatment of Nephrotic Syndrome

Abstract.The nephrotic syndrome, caused by glomerulonephritis, diabetes mellitus, or amyloidosis, is still a therapeutic challenge. Newer therapeutic approaches may be sought in the fields of immunosuppression, nonspecific supportive measures, heparinoid administration, and removal of a supposed glomerular basement membrane toxic factor. In immunosuppression, the newer drugs now used in organ transplantation (cyclosporine, tacrolimus, and mycophenolate mofetil) can also be used in the treatment of glomerulonephritis. In nonspecific supportive treatment, angiotensin II receptor antagonists are now used in addition to angiotensin-converting enzyme inhibitors. Positive effects of hydroxymethylglutaryl coenzyme A reductase inhibitors on the nephrotic syndrome have not yet been proven. Cyclooxygenase II inhibitors must be tested but probably have too many renal side effects, similar to those of nonsteroidal anti-inflammatory drugs. Heparinoids or glycosaminoglycans serve as polyanions and thus have protective effects on the negative charge of the glomerular basement membrane. They can now be administered as oral medications. The removal of a supposed glomerular basement membrane toxic factor that induces proteinuria has been attempted for 20 yr and now is usually performed using immunoadsorption. Especially in cases of recurrent nephrotic syndrome after renal transplantation for patients with glomerulonephritis, this approach has been successful in decreasing proteinuria, although in most cases its effect is not lasting but must be continuously renewed.

Recurrence of Nephrotic Syndrome after Transplantation in CNF Is due to Autoantibodies to Nephrin

The novel gene NPHS1 is defective in the patients with congenital nephrotic syndrome of the Finnish type (CNF) leading to abnormal expression of the respective protein product nephrin in glomerular cells. CNF patients are treated with early nephrectomy and renal transplantation, but about 20% show recurrence of nephrotic syndrome (NS). We used indirect immunofluorescence microscopy and immunoblotting and an ELISA assay to search for circulating autoantibodies to nephrin, the protein defect in CNF patient kidneys. In serial serum samples gathered before and after recurrence of NS, we show an increased antibody titer to nephrin prior to the NS episode and a subsequent drop in antibody level after its successful treatment and reactivity of the high titer sera with glomeruli in indirect immunofluorescence microscopy as well. The results show that the transplantation treatment introduces a neoantigen inducing production of autoantibodies, which may be pathogenic for perturbation of the function of the glomerular filtration barrier.

Convulsion during cyclosporin A therapy for nephrotic syndrome

A 10-year-old boy with nephrotic syndrome developed convulsions 6 weeks after the start of cyclosporin A (CyA) therapy. Generalized tonic-clonic convulsion occurred during relapse of nephrotic syndrome after influenza A infection. T2-weighted magnetic resonance imaging (MRI) showed high signal intensities in bilateral parieto-occipital lobes. He recovered from the convulsions and the MRI findings returned to normal early without neurological sequelae. CyA was discontinued for 1 week and then restarted. He has had no further convulsions or recurrence of nephrotic syndrome since that time. He had no evidence of high blood level of CyA, hypertension, electrolyte abnormalities, or renal or hepatic dysfunction. He was diagnosed with CyA-related reversible posterior leukoencephalopathy syndrome based on the rapid recovery of clinical symptoms and the characteristic MRI finding. Influenza A infection may have damaged the blood-brain barrier, paving the way for central nervous system toxicity.