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Articles by N Leung
Total Records ( 8 ) for N Leung
  C. U Lee , C. M Wood , G. K Hesley , N Leung , M. D Bridges , J. T Lund , P. U Lee and M. R. Pittelkow

Objectives  To estimate and stratify the risk of development of nephrogenic systemic fibrosis (NSF) in well-defined at-risk subpopulations from a large single institution, and to perform a single-institution case series study of patients with biopsy-proven NSF.

Design  Retrospective cohort of patients exposed to gadolinium-based contrast agents (GBCAs) at a single institution during an 8-year period (January 1, 1999, to December 31, 2006), and a case series study of patients with biopsy-proven NSF.

Setting  A primary, secondary, and tertiary health care center that treated more than 2.2 million outpatients and had 135 000 hospital admissions in 2007.

Patients  A total of 94 917 patients exposed to GBCAs; patients at risk for NSF (3779 patients on hemodialysis, 1694 patients with renal transplants, and 717 patients with liver transplants, a well-defined subgroup that includes patients at risk for reduced renal function); and 61 patients with a clinical diagnosis of NSF.

Main Outcome Measure  Risk estimate for NSF.

Results  The risk of development of NSF is 1.0% for patients who undergo hemodialysis (8 of 827), 0.8% for patients with renal transplantation (4 of 527), and 0% for patients with liver transplantation at our institution (0 of 327).

Conclusions  Despite the limitations, this study, which reviewed a large number of patients who underwent intravascular GBCA injections, demonstrates a 77-fold higher risk of NSF among patients who undergo hemodialysis and a 69-fold higher risk in patients with renal transplantation. This increased risk is thought to be associated with poor clearance of most GBCAs.

  F Silva , U Specks , S Kalra , M. C Hogan , N Leung , S Sethi and F. C. Fervenza

Background and objectives: Microscopic polyangiitis (MPA) is a systemic small-vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA), often targeting myeloperoxidase (MPO). Cyclophosphamide (CYC) plus corticosteroids (CS) is considered standard therapy for patients with renal involvement, but treatment response is not satisfactory in all patients and CYC has well recognized toxicity. This prospective pilot trial explored whether mycophenolate mofetil (MMF) represents an effective alternative to CYC for induction and maintenance of remission in MPA with mild to moderate renal involvement.

Design, setting, participants, & measurements: Seventeen P-ANCA/MPO-ANCA-positive patients with MPA with mild to moderate renal involvement received MMF (1000 mg orally, twice daily) and CS (intravenous methylprednisolone, 1 to 3 g, followed by oral prednisone at 1 mg/kg per day). Oral CS were discontinued by month 6; MMF was continued through month 18. The primary outcome measure was remission by month 6 and stable renal function. Secondary endpoints included major relapses necessitating a switch to CYC plus CS, minor relapses requiring an increase in CS dosage, and adverse events.

Results: Thirteen of 17 patients enrolled achieved the primary outcome, and 4 failed because of insufficient response, relapse, or MMF intolerance. Twelve patients remained in remission through month 18, renal function remained stable, and proteinuria improved. Side effects of MMF were mild, transient, and responsive to dose adjustments in all patients except one.

Conclusions: MMF represents an alternative to CYC for induction and maintenance of remission in patients with MPO-ANCA-associated MPA with mild to moderate renal disease.

  S Sethi , L Zand , N Leung , R. J. H Smith , D Jevremonic , S. S Herrmann and F. C. Fervenza

Background and objectives: Membranoproliferative glomerulonephritis (MPGN) is an immune complex–mediated glomerulonephritis characterized by subendothelial and mesangial deposition of immune complexes. Autoimmune diseases and chronic infections, such as hepatitis C, are commonly recognized causes of MPGN; however, monoclonal gammopathy is a less widely recognized cause of MPGN.

Design, setting, participants, & measurements: We reviewed all renal biopsies of MPGN in Mayo Clinic patients during a 6-year period to determine the association of monoclonal gammopathy with MPGN. Results were correlated with electrophoresis studies and bone marrow biopsies to clarify the relationship between MPGN and gammopathies.

Results: Of 126 patients with MPGN, 20 did not have workup for hepatitis B or C. Of the remaining 106 patients, 25 (23.5%) were positive for hepatitis B or C. Of the 81 hepatitis-negative patients, 13 were not evaluated for gammopathies. Of the remaining 68 patients, 28 (41.1%) had serum and/or urine electrophoresis studies positive for monoclonal gammopathy. Serum immunofixation electrophoresis was the most sensitive method for diagnosing monoclonal gammopathy. Renal biopsy showed a membranoproliferative pattern of injury; immunofluorescence microscopy was often instrumental in diagnosing the underlying gammopathy. On the basis of the bone marrow biopsy, monoclonal gammopathy of undetermined significance was the most common entity associated with MPGN. Other, less common causes included multiple myeloma, low-grade B cell lymphoma, and chronic lymphocytic leukemia.

Conclusions: Monoclonal gammopathy is an important and common cause of MPGN; therefore, all patients with a diagnosis of MPGN should be evaluated for an underlying monoclonal gammopathy.

  S Sethi , J. D Theis , N Leung , A Dispenzieri , S. H Nasr , M. E Fidler , L. D Cornell , J. D Gamez , J. A Vrana and A. Dogan

Background and objectives: Amyloidosis is a group of disorders characterized by accumulation of extracellular deposition of proteins as insoluble aggregates. The clinical management of amyloidosis is based on identifying the underlying etiology and accurate typing of the amyloid. Ig heavy chain amyloid involving the kidney is poorly recognized and often poses a diagnostic dilemma.

Design, setting, participants, & measures: In this study, we describe the use of laser microdissection (LMD) and mass spectrometry (MS)–based proteomic analysis for the accurate typing of 14 cases of amyloidosis. We also describe the clinicopathologic findings of four problematic cases of renal Ig heavy chain amyloidosis that required LMD/MS proteomic analysis for accurate typing of the amyloid.

Results: LMD/MS proteomic data of four cases of Ig heavy chain renal amyloidosis showed Ig heavy chains with or without light chains. The break up of the Ig heavy chains was as follows: one case showed Ig1 chain constant region and light chains, one case showed Ig chain constant region and light chains variable and constant regions, whereas two cases showed Ig3 chain constant region and heavy chains variable region I and/or III without light chains. We compare the LMD/MS proteomic data of Ig heavy chain renal amyloid with that of other types of amyloid, including Ig light chains, serum amyloid A, fibrinogen A- chain renal amyloid, and transthyretin amyloid.

Conclusions: We conclude that LMD/MS is a sensitive and specific tool for diagnosis and accurate typing of renal amyloidosis, including Ig heavy chain amyloid.

  F. C Fervenza , R. S Abraham , S. B Erickson , M. V Irazabal , A Eirin , U Specks , P. H Nachman , E. J Bergstralh , N Leung , F. G Cosio , M. C Hogan , J. J Dillon , L. J Hickson , X Li , D. C Cattran and for the Mayo Nephrology Collaborative Group

Background and objectives: It was postulated that in patients with membranous nephropathy (MN), four weekly doses of Rituximab (RTX) would result in more effective B cell depletion, a higher remission rate, and maintaining the same safety profile compared with patients treated with RTX dosed at 1 g every 2 weeks. This hypothesis was supported by previous pharmacokinetic (PK) analysis showing that RTX levels in the two-dose regimen were 50% lower compared with nonproteinuric patients, which could potentially result in undertreatment.

Design, setting, participants, & measurements: Twenty patients with MN and proteinuria >5 g/24 h received RTX (375 mg/m2 x 4), with re-treatment at 6 months regardless of proteinuria response. PK analysis was conducted simultaneously with immunological analyses of T and B cells to ascertain the effect of RTX on lymphocyte subpopulations.

Results: Baseline proteinuria of 11.9 g/24 h decreased to 4.2 and 2.0 g/24 h at 12 and 24 months, respectively, whereas creatinine clearance increased from 72.4 ml/min per 1.73 m2 at baseline to 88.4 ml/min per 1.73 m2 at 24 months. Of 18 patients who completed 24-month follow-up, 4 are in complete remission, 12 are in partial remission, 1 has a limited response, and 1 patient relapsed. Serum RTX levels were similar to those obtained with two doses of RTX.

Conclusions: Four doses of RTX resulted in more effective B cell depletion, but proteinuria reduction was similar to RTX at 1 g every 2 weeks. Baseline quantification of lymphocyte subpopulations did not predict response to RTX therapy.

  N Leung , N. A Saucier , S. R Zeldenrust , H. D Gunderson and L. D. Cornell

Sunitinib is a multiple tyrosine kinase receptors inhibitor that is approved for the treatment of advanced renal cell carcinoma. Amongst its targets are fetal liver tyrosine kinase receptor 3 (FLT 3) and vascular endothelial growth factor receptor (VEGFR). Renal toxicity has not been reported from the trials, but several patients have been reported to develop a pre-eclampsia-like syndrome. We report the first case of acute tubular necrosis in a patient with multiple myeloma following treatment with sunitinib.

  N Leung , M. R Pittelkow , C. U Lee , J. A Good , M. M Hanley and T. P. Moyer

A 65-year-old female with biopsy-confirmed nephrogenic systemic fibrosis (NSF) received a kidney transplantation. Despite good kidney function, her symptoms continued to progress. Deferoxamine was administered intramuscularly at 500 mg/day and later 1000 mg/day after 1 week with no adverse effects. Urine excretion of gadolinium increased from 6.0 µg/day to 11.6 µg/day and subsequently to 13.0 µg/day with 500 mg/day and 1000 mg/day of deferoxamine, respectively. Serum levels, however, remain unchanged from 1.7 ng/ml to 1.4 ng/ml. Although chelation therapy may have a role in the treatment of NSF, deferoxamine is too weak and a stronger chelator is needed.

  N Leung , F. K Buadi , K. W Song , A. B Magil and L. D. Cornell

Cryocrystalglobulinaemia is an extremely rare complication of monoclonal gammopathy. Its presentation has features of both type I and II cryoglobulinaemia. Although peripheral and digital ischaemia is common, visceral ischaemia is rare. When it does occur, it is usually associated with multiple myeloma and has an extremely poor prognosis. We present a case of bilateral renal artery thrombosis associated with cryocrystalglobulinaemia in a patient without myeloma. More unusual, the cryocrystal protein in this case was associated with fibrinogen, which may have led to increased propensity towards thrombosis. Although the patient was unable to recover his kidney function, he remained alive on dialysis 2 years after the incident. The patient did not have any further ischaemic event despite no definitive therapy. This case represents an unusual presentation for this rare disease.

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