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Articles by M. C Hogan
Total Records ( 3 ) for M. C Hogan
  A. B Chapman , V. E Torres , R. D Perrone , T. I Steinman , K. T Bae , J. P Miller , D. C Miskulin , F. R Oskoui , A Masoumi , M. C Hogan , F. T Winklhofer , W Braun , P. A Thompson , C. M Meyers , C Kelleher and R. W. Schrier
 

Background and objectives: Two HALT PKD trials will investigate interventions that potentially slow kidney disease progression in hypertensive autosomal dominant polycystic kidney disease (ADPKD) patients. Studies were designed in early and later stages of ADPKD to assess the impact of intensive blockade of the renin-angiotensin-aldosterone system and level of BP control on progressive renal disease.

Design, settings, participants, and measurements: PKD-HALT trials are multicenter, randomized, double-blind, placebo-controlled trials studying 1018 hypertensive ADPKD patients enrolled over 3 yr with 4 to 8 yr of follow-up. In study A, 548 participants, estimated GFR (eGFR) of >60 ml/min per 1.73 m2 were randomized to one of four arms in a 2-by-2 design: combination angiotensin converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) therapy versus ACEi monotherapy at two levels of BP control. In study B, 470 participants, eGFR of 25 to 60 ml/min per 1.73 m2 compared ACEi/ARB therapy versus ACEi monotherapy, with BP control of 120 to 130/70 to 80 mmHg. Primary outcomes of studies A and B are MR-based percent change kidney volume and a composite endpoint of time to 50% reduction of baseline estimated eGFR, ESRD, or death, respectively.

Results: This report describes design issues related to (1) novel endpoints such as kidney volume, (2) home versus office BP measures, and (3) the impact of RAAS inhibition on kidney and patient outcomes, safety, and quality of life.

Conclusions: HALT PKD will evaluate potential benefits of rigorous BP control and inhibition of the renin-angiotensin-aldosterone system on kidney disease progression in ADPKD.

  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.

  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.

 
 
 
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