PubMed Health⌕ Search

Biomedical subjects

Nelson Leung

Publications and source records attributed to Nelson Leung.

17 recordsLinked to original sources
PubMed2006

A proliferative glomerulonephritis secondary to a monoclonal IgA.

A distinct entity mimicking immune-complex-mediated glomerulonephritis characterized by a proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits recently was described. We now report a case of a 35-year-old woman who presented with sudden onset of edema, proteinuria, hematuria, and hypertension. Renal biopsy showed diffuse endocapillary proliferation, mesangial cellularity, and amorphous material in the mesangium. Immunofluorescence examination showed mesangial and capillary wall staining for IgA (2+), C3 (2+), fibrinogen (2+), and lambda (2+). Congo red stain was negative. Electron microscopy showed mesangial and subendothelial deposits with a paracrystalline lattice-like substructure forming parallel linear arrays. Extensive laboratory evaluation showed a small population of monoclonal plasma cells with lambda restriction. The present case suggests that monoclonal IgA deposits also can cause proliferative glomerulonephritis. However, the presence of paracrystalline deposits in association with monoclonal IgA deposits has not been described previously.

Adult↗
PubMed2005

Excessive fluid accumulation during stem cell mobilization: a novel prognostic factor of first-year survival after stem cell transplantation in AL amyloidosis patients.

High-dose melphalan followed by stem cell transplantation (HDM-SCT) has become the treatment of choice for patients with immunoglobulin light chain amyloidosis (AL). Unfortunately, treatment mortality can be excessive in certain subpopulations. We have noted that patients who gained more than 2% body weight during mobilization had a poorer outcome following HDM-SCT. Excluding 2 patients for lack of weight record and denial of consent, 126 patients between July 1997 and June 2003 were retrospectively studied. Weight increased more than 2.0% during mobilization in 51.6% of the patients. Patients who accumulated more than 2.0% tended to have more proteinuria, more organs involved, lower serum albumin, more diuretic use, and dosage adjustment during mobilization. First-year mortality was significantly higher in those with more than 2% weight gain (33.9% versus 9.8%, P = .002). Multivariate analysis showed weight gain, glomerular filtration rate, and septal thickness to be independent predictors of first-year mortality. The increase in mortality was noted even after the excess weight was diuresed prior to conditioning. The impact on mortality dissipated after the first year. Weight gain during mobilization appears to be a new marker of adverse outcome following HDM-SCT. Better prognostication may improve the treatment mortality rate of these patients.

Adult↗
PubMed2005

Acute renal insufficiency after high-dose melphalan in patients with primary systemic amyloidosis during stem cell transplantation.

BACKGROUND: Patients with primary systemic amyloidosis (AL) have a poor prognosis. Median survival time from standard treatments is only 17 months. High-dose intravenous melphalan followed by peripheral blood stem cell transplant (PBSCT) appears to be the most promising therapy, but treatment mortality can be high. The authors have noted the development of acute renal insufficiency immediately after melphalan conditioning. This study was undertaken to further examine its risk factors and impact on posttransplant mortality. METHODS: Consecutive AL patients who underwent PBSCT were studied retrospectively. Acute renal insufficiency (ARI) after high-dose melphalan was defined by a minimum increase of 0.5 mg/dL (44 micromol/L) in the serum creatinine level that is greater than 50% of baseline immediately after conditioning. Urine sediment score was the sum of the individual types of sediment identified on urine microscopy. RESULTS: Of the 80 patients studied, ARI developed in 18.8% of the patients after high-dose melphalan. Univariate analysis identified age, hypoalbuminemia, heavy proteinuria, diuretic use, and urine sediment score (>3) as risk factors. Age and urine sediment score remained independently significant risk factors in the multivariate analysis. Patients who had ARI after high-dose melphalan underwent dialysis more often (P = 0.007), and had a worse 1-year survival (P = 0.03). CONCLUSION: The timing of renal injury strongly suggests melphalan as the causative agent. Ongoing tubular injury may be a prerequisite for renal injury by melphalan as evidenced by the active urinary sediment. Development of ARI adversely affected the outcome after PBSCT. Effective preventive measures may help decrease the treatment mortality of PBSCT in AL patients.

Acute Kidney Injury↗
PubMed2005

Recurrent Goodpasture's disease secondary to a monoclonal IgA1-kappa antibody autoreactive with the alpha1/alpha2 chains of type IV collagen.

Goodpasture's disease is characterized by crescentic glomerulonephritis and lung hemorrhage in the presence of anti-glomerular basement membrane (anti-GBM) antibodies. This disease usually is mediated by IgG autoantibodies directed against the noncollagenous domain of the alpha3(IV) collagen chain, the Goodpasture autoantigen. In rare cases, anti-GBM antibodies of IgA or IgM class are involved, but their specificity has not been determined, and their target antigen remains unknown. The authors present the case of a 62-year-old man with anti-GBM disease mediated by a monoclonal IgA-kappa antibody, which progressed to end-stage renal disease despite intensive immunosuppression. The patient underwent living-related kidney transplantation, but lung hemorrhage and crescentic glomerulonephritis recurred, causing the loss of the allograft 2 years later. Indirect immunofluorescence found the presence of circulating IgA antibodies reactive with a basement membrane component, identified by enzyme-linked immunoabsorbent assay and Western blot as the alpha1/alpha2(IV) collagen chains. Sensitivity to digestion with collagenase indicated that IgA bound to epitopes located in the collagenous domain. This is the first case of recurrent Goodpasture's disease secondary to an autoreactive IgA antibody. The specificity of an IgA antibody implicated in the pathogenesis of anti-GBM disease has been investigated for the first time, identifying the alpha1/alpha2(IV) collagen chains as a novel target for nephritogenic antibodies.

Anti-Glomerular Basement Membrane Disease↗
PubMed2005

Renal response after high-dose melphalan and stem cell transplantation is a favorable marker in patients with primary systemic amyloidosis.

BACKGROUND: Primary systemic (AL) amyloidosis is a rare plasma cell disorder characterized by soft-tissue deposition of monoclonal light chain fragments. High-dose melphalan followed by autologous stem cell transplantation currently has become the treatment of choice. Favorable outcome is ensured with achievement of hematologic response, but little is known about organ response. This study was undertaken to determine the prognostic importance of renal response after high-dose melphalan and stem cell transplantation. METHODS: All patients with AL amyloidosis who underwent autologous stem cell transplantation between 1996 and December 2002 were selected for study. Renal response is defined as a 50% or greater reduction in proteinuria with less than 25% decline in renal function. Exclusion criteria included pretransplantation dialysis therapy or dialysis dependence posttransplantation, treatment mortality, lack of proteinuria assessment posttransplantation, and baseline proteinuria with protein less than 1 g/d. RESULTS: Of 105 patients, 47 were excluded for stated reasons. Renal response was achieved in 60.3% of evaluated patients. Proteinuria was reduced by greater than 90% in 37.9% and returned to normal in 15.5%. Median response time was 12 months. Renal response was associated with a greater increase in serum albumin level (P = 0.001), maintenance of renal function (P < 0.001), and better survival (P = 0.0003). Renal responders had better survival regardless of hematologic response (P = 0.01 to 0.05). CONCLUSION: Currently, high-dose melphalan followed by stem cell transplantation is the most effective treatment for AL amyloidosis for those who are eligible. Our data show that renal response after high-dose melphalan followed by stem cell transplantation is associated with improved survival. Renal response is an independent marker of treatment success and can be used in cases in which determination of hematologic response is difficult.

Adult↗
PubMed2005

Acute granulomatous interstitial nephritis secondary to bisphosphonate alendronate sodium.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and is characterized by a progressive accumulation of functionally incompetent monoclonal lymphocytes. Renal involvement has been described in CLL but is uncommon. Granulomatous interstitial nephritis is a rare but characteristic hallmark of certain diseases such as sarcoidosis and tuberculosis. These epithelial reactions have also been reported with medications, infections, inflammation, Wegener's granulomatosis, and jejunoileal bypass. We present a 74-year-old woman with a stage 0 chronic lymphocytic leukemia who developed acute renal failure following the initiation of alendronate. The renal biopsy revealed an acute granulomatous interstitial nephritis. Infectious and inflammatory etiologies were ruled out. Hemodialysis was required despite discontinuation of all medications. Partial recovery of renal function occurred after 6 weeks of prednisone therapy and cyclophosphamide. This report describes a unique case of acute granulomatous interstitial nephritis and leukemic cell kidney infiltration by CLL.

Acute Disease↗
PubMed2005

Myeloablative chemotherapy and stem cell transplantation in myeloma or primary amyloidosis with renal involvement.

BACKGROUND: High-dose chemotherapy and stem cell transplantation are being applied increasingly to the treatment of selected patients with multiple myeloma or primary systemic amyloidosis. Stem cell transplantation presents unique challenges to the nephrologist because of the high prevalence of renal involvement in myeloma and the issues that are associated with high-dose chemotherapy in patients with the nephrotic syndrome due to renal amyloid. METHODS: We review the published literature on stem cell transplantation in patients with reduced renal function. RESULTS AND CONCLUSIONS: The specifics of transplantation pertaining to patients with renal amyloid nephrotic syndrome are discussed in detail.

Amyloidosis↗
PubMed2005

Living donor kidney and autologous stem cell transplantation for primary systemic amyloidosis (AL) with predominant renal involvement.

Primary systemic amyloidosis (AL) is characterized by multiorgan deposition of monoclonal immunoglobulin light chain. Renal involvement is common and impaired kidney function is associated with reduced median survival. Autologous stem cell transplantation (SCT) for AL achieves superior response rates compared to chemotherapy alone but patients with end-stage renal disease (ESRD) may be excluded from consideration. A treatment approach consisting of living donor kidney transplantation (LDKTx) followed by autologous SCT was developed for AL with ESRD. Eight patients underwent LDKTx with immediate graft function. Two suffered unanticipated complications post-KTx and died 10 and 3 months later. Two cases of subclinical acute cellular rejection (ACR) and one case of clinical ACR occurred--all reversible with corticosteroid. Six patients had successful stem cell harvests performed and five of these underwent SCT with satisfactory trilineage engraftment. Renal function remained stable following SCT in four and was reduced in one due to infectious and bleeding complications. One patient, who has thus far elected not to undergo SCT, has proteinuria and histologic evidence of recurrent renal amyloidosis. This experience supports the feasibility of sequential living donor KTx and autologous SCT for carefully selected patients with ESRD due to AL.

Adolescent↗
PubMed2004

Long-term outcome of renal transplantation in light-chain deposition disease.

BACKGROUND: Light-chain deposition disease (LCDD) is a monoclonal gammopathy characterized by nonamyloid deposition of light chain in various organs. A small number of kidney transplantations have been performed on LCDD patients in whom end-stage renal disease (ESRD) developed. METHODS: The authors retrospectively reviewed the clinical and histologic findings and outcome of 7 patients with LCDD who underwent kidney transplantation at our institution. RESULTS: Renal insufficiency, hypertension, and proteinuria were present in all 7 patients. Proteinuria level was greater than 3.5 g/24 h in 3 patients. Three patients had microscopic hematuria. Monoclonal protein was detected in the serum in 3 patients, urine in 5, and was undetectable in 2. Median age at presentation was 42.7 (range, 33 to 58) years. The most common renal biopsy findings were mesangial expansion, mesangial nodules, tubular basement membrane thickening, and tubular atrophy. Kappa light chain was detected in all 7 renal biopsy results. Five patients were on dialysis before transplantation. LCDD recurred after a median of 33.3 (range, 2 to 45) months in 5 of the 7 patients. One patient remains on dialysis, whereas the other 4 have died. One patient died of progression of multiple myeloma 3 months after kidney transplantation without evidence of recurrence. Only 1 patient remains recurrence free after 13 years with normal renal allograft function. CONCLUSION: Although long-term benefits are occasionally seen, renal allograft survival is reduced significantly in LCDD patients. Kidney transplantation should not be an option for LCDD patients unless measures have been taken to reduce light chain production.

Adult↗
PubMed2004

A novel alpha-galactosidase a mutant (M42L) identified in a renal variant of Fabry disease.

A 65-year-old man presented to our institution for workup of proteinuria. His serum creatinine level was 1.7 mg/dL (130 micromol/L), and he had proteinuria with protein of almost 5 g/24 h. Fabry disease was diagnosed by means of kidney biopsy and low serum and leukocyte levels of alpha-galactosidase A. Review of his history, family history, physical examinations, and diagnostic studies did not show other findings typical of this disease. His renal function continued to decline, and he eventually underwent a living unrelated renal transplantation 5 years later. Three years after transplantation, his creatinine level is 1.7 mg/dL (130 micromol/L), and corrected iothalamate clearance is 53 mL/min/1.73 m2 . Genetic studies showed that he has a novel missense mutation (M42L) in exon 1. Methionine at codon 42 is highly conserved in eukaryotic alpha-galactosidase A orthologues. This genotype predicts a minor misfolding of alpha-galactosidase A because of a small difference in hydrophobicity between methionine and leucine. His mutation resulted in a very low, but detectable, serum level of alpha-galactosidase A (0.002 U/L; normal range, 0.016 to 0.2 U/L). Cases of Fabry disease that present with predominantly renal manifestations are rare and require a high index of suspicion for diagnosis. Because treatment for Fabry disease recently has become available, it is important for clinicians to be aware of this disease and pursue the diagnosis in cases of otherwise unexplained renal dysfunction.

Aged↗
PubMed2002

A tale of two markers.

Explore the source record for details and available documents.

Cerebrospinal Fluid Proteins↗
PubMed2002

Chronic renal dysfunction late after liver transplantation.

With the increasing success of liver transplantation, more patients are developing late complications such as renal dysfunction. The goal of the current study was to assess the prevalence of renal dysfunction years after liver transplantation and to identify patients at risk for the development of this complication. Of the 527 liver transplantations performed at our institution between April 1990 and October 1998, 353 had pretransplantation and posttransplantation glomerular filtration rate (GFR) determinations by iothalamate clearance. From this entire group, 198 patients had actual 4-year follow-up and 52 had actual 6-year follow-up. In addition, 191 of these patients had intensive follow-up with GFR measurements pretransplantation and at 1 and 3 years posttransplantation (complete follow-up group). All patients received either tacrolimus- or cyclosporine-based immunosuppression. The overall mean GFR levels in both of these groups was acceptable and was not different in cyclosporine- versus tacrolimus-based immunosuppressive regimens. Renal dysfunction was progressive, with 27.5% of patients in the intensive group having a GFR < 40 mL/min/body surface area 5 years after transplantation. GFR pretransplantation did not correlate well with late renal function; however, GFR at 1 year identified patients with subsequent renal dysfunction. The cumulative incidence of renal failure for the entire group was 6.25% at 7 years and 10% at 10 years. Renal dysfunction is a major late complication after liver transplantation. The GFR at 1 year correlates best with late renal function. Patients with a low GFR at 1 year (< 40 mL/min/BSA) are a high-risk group that might benefit from early therapeutic interventions aimed at preventing subsequent renal failure.

Chronic Disease↗