Publications by authors named "Michael B Stokes"

55 Publications

Computed tomography and atrial fibrillation substrate: The knowns and unknowns.

Trends Cardiovasc Med 2020 Nov 20. Epub 2020 Nov 20.

Centre for Heart Rhythm Disorders (CHRD), University of Adelaide and Royal Adelaide Hospital, Adelaide, SA 5000, Australia. Electronic address:

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http://dx.doi.org/10.1016/j.tcm.2020.11.005DOI Listing
November 2020

Association of HLA Typing and Alloimmunity With Posttransplantation Membranous Nephropathy: A Multicenter Case Series.

Am J Kidney Dis 2020 09 28;76(3):374-383. Epub 2020 Apr 28.

Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY.

Rationale & Objectives: Posttransplantation membranous nephropathy (MN) represents a rare complication of kidney transplantation that can be classified as recurrent or de novo. The clinical, pathologic, and immunogenetic characteristics of posttransplantation MN and the differences between de novo and recurrent MN are not well understood.

Study Design: Multicenter case series.

Setting & Participants: We included 77 patients from 5 North American and European medical centers with post-kidney transplantation MN (27 de novo and 50 recurrent). Patients with MN in the native kidney who received kidney allografts but did not develop recurrent MN were used as nonrecurrent controls (n = 43). To improve understanding of posttransplantation MN, we compared de novo MN with recurrent MN and then contrasted recurrent MN with nonrecurrent controls.

Findings: Compared with recurrent MN, de novo MN was less likely to be classified as primary MN (OR, 0.04; P < 0.001) and had more concurrent antibody-mediated rejection (OR, 12.0; P < 0.001) and inferior allograft survival (HR for allograft failure, 3.2; P = 0.007). HLA-DQ2 and HLA-DR17 antigens were more common in recipients with recurrent MN compared with those with de novo MN; however, the frequency of these recipient antigens in recurrent MN was similar to that in nonrecurrent MN controls. Among the 93 kidney transplant recipients with native kidney failure attributed to MN, older recipient age (HR per each year older, 1.03; P = 0.02), recipient HLA-A3 antigen (HR, 2.5; P = 0.003), steroid-free immunosuppressive regimens (HR, 2.84; P < 0.001), and living related allograft (HR, 1.94; P = 0.03) were predictors of MN recurrence.

Limitations: Retrospective case series, limited sample size due to rarity of the disease, nonstandardized nature of data collection and biopsies.

Conclusions: De novo and recurrent MN likely represent separate diseases. De novo MN is associated with humoral alloimmunity and guarded outcome. Potential predisposing factors for recurrent MN include recipients who are older, recipient HLA-A3 antigen, steroid-free immunosuppressive regimen, and living related donor kidney.
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http://dx.doi.org/10.1053/j.ajkd.2020.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483441PMC
September 2020

Classification of Lupus Nephritis; Time for a Change?

Adv Chronic Kidney Dis 2019 09;26(5):323-329

Columbia University College of Physicians and Surgeons, New York, NY.

Renal biopsy plays a critical role in the diagnosis and management of kidney disease in patients with systemic lupus erythematosus. The current pathologic classification of lupus nephritis is widely accepted but remains a work in progress. We discuss the key challenges in lupus nephritis classification and review new approaches to improve clinical utility and prognostic value.
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http://dx.doi.org/10.1053/j.ackd.2019.06.002DOI Listing
September 2019

Bodyweight fluctuation and atrial fibrillation: A new risk factor?

Heart Rhythm 2020 03 25;17(3):372-373. Epub 2019 Oct 25.

Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, Adelaide, South Australia. Electronic address:

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http://dx.doi.org/10.1016/j.hrthm.2019.10.023DOI Listing
March 2020

Cardiac involvement in idiopathic inflammatory myopathies detected by cardiac magnetic resonance imaging.

Clin Rheumatol 2019 Dec 19;38(12):3471-3476. Epub 2019 Jul 19.

Rheumatology Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

Cardiac involvement in idiopathic inflammatory myopathies (IIM) adversely affects prognosis but is commonly sub-clinical. Cardiac magnetic resonance imaging (CMR) is an effective imaging modality for detecting myocardial inflammation and fibrosis but its use as a screening tool for cardiac disease in IIM has not been fully explored. Nineteen patients with IIM without cardiac symptoms underwent CMR using a specific cardiomyopathy protocol including specific sequences detecting focal and diffuse myocardial fibrosis. 9/19 patients demonstrated late gadolinium enhancement (LGE (3/9 right ventricular insertion, 1/9 sub-endocardial, 7/9 mid-wall/sub-epicardial)). T1 mapping was performed in 15 patients. In total, 7/15 had elevated native T1 values, of which four had detected LGE. Myocardial fibrosis was frequently detected in IIM patients without cardiac history. Detection of LGE and elevated T1 values may have negative prognostic implications. Longitudinal studies determining whether early or augmented treatment has a role in patients with sub-clinical cardiac involvement are needed.Key Points• Cardiac involvement in myositis adversely affects prognosis.• Cardiac magnetic resonance imaging is an effective tool for detecting cardiac involvement.• T1 mapping is a technique which detects diffuse myocardial inflammation and fibrosis.• In our study, focal and diffuse myocardial fibrosis was frequently found in myositis patients without cardiac symptoms.
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http://dx.doi.org/10.1007/s10067-019-04678-zDOI Listing
December 2019

Effects of Arteriovenous Fistula Ligation on Cardiac Structure and Function in Kidney Transplant Recipients.

Circulation 2019 06 2;139(25):2809-2818. Epub 2019 May 2.

Adelaide Medical School, University of Adelaide, Australia (N.N.R., S.U., R.P.C., S.P.M., M.I.W., P.T.C.).

Background: Cardiovascular morbidity and mortality remain high in recipients of a kidney transplant. The persistence of a patent arteriovenous fistula (AVF) after transplantation may contribute to ongoing maladaptive cardiovascular remodeling. The ability to reverse this maladaptive remodeling by ligation of this AVF is unknown. We conducted the first randomized controlled trial to evaluate the effect of AVF ligation on cardiac structure and function in stable kidney transplant recipients.

Methods: In this randomized controlled trial, kidney transplant recipients (>12 months after transplantation with stable graft function) were randomized to AVF ligation or no intervention. All participants underwent cardiac magnetic resonance imaging at baseline and at 6 months. The primary outcome was the change in left ventricular (LV) mass. Secondary outcomes included changes in LV volumes, left and right atrial areas, LV ejection fraction, NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, cardiac output/index, brachial flows (ipsilateral to AVF), and pulmonary artery velocity.

Results: A total of 93 patients were screened, of whom 64 met the inclusion criteria and were randomized to the AVF ligation (n=33) or control (n=31) group. Fifty-four participants completed the study: 27 in the AVF ligation group and 27 in the control group. On the second cardiac magnetic resonance scan, a mean decrease of 22.1 g (95% CI, 15.0-29.1) was observed in LV mass in the AVF ligation group compared with a small increase of 1.2 g (95% CI, -4.8 to 7.2) in the control group ( P<0.001). Significant decreases in LV end-diastolic volumes, LV end-systolic volumes, cardiac output, cardiac index, atrial volumes, and NT-proBNP were also seen in the AVF closure group ( P<0.01). No significant changes were observed in LV ejection fraction ( P=0.93) and pulmonary artery velocity ( P=0.07). No significant complications were noted after AVF ligation. No changes in estimated glomerular filtration rate or systolic and diastolic blood pressures were observed between cardiac magnetic resonance scans.

Conclusions: Elective ligation of patent AVF in adults with stable kidney transplant function resulted in clinically significant reduction of LV myocardial mass.

Clinical Trial Registration: Australian and New Zealand Clinical Trials Registry URL: https://www.anzctr.org.au . Unique Identifier: ACTRN12613001302741.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.038505DOI Listing
June 2019

Does Left Ventricular Systolic Function Matter? Treating Atrial Fibrillation in HFrEF Versus HFpEF.

Cardiol Clin 2019 May;37(2):157-166

Department of Cardiology, Centre for Heart Rhythm Disorders, South Australian Health and Medical Research Institute, University of Adelaide, Royal Adelaide Hospital, Port Road, Adelaide, South Australia 5000, Australia. Electronic address:

Atrial fibrillation (AF) and heart failure (HF) pose international health care challenges that contribute significantly to hospitalizations, morbidity, mortality, and significant health care costs. Both AF and HF contribute to the development of each other and both are associated with a worsened prognosis when they occur together. Assessment of systolic function via transthoracic echocardiography is essential in the investigation of the AF patient. Clinical and echocardiographic assessment may classify AF patients with HF into HF with reduced ejection fraction (HF-rEF) and HF with preserved ejection fraction (HF-pEF). Such classification can assist in numerous important management decisions in AF.
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http://dx.doi.org/10.1016/j.ccl.2019.01.008DOI Listing
May 2019

Bilateral acute non-obstructive pyelonephritis presenting as acute kidney injury requiring haemodialysis.

BMJ Case Rep 2019 Feb 21;12(2). Epub 2019 Feb 21.

Division of Nephrology, Department of Internal Medicine, Bronx-Lebanon Hospital Center, Bronx, New York, USA.

A 54-year-old female patient with hypothyroidism and diabetes mellitus type 2 was brought to emergency room by the family members for acute change in mental status. The laboratory evaluation demonstrated findings consistent with acute renal failure (normal renal function 3 months prior to presentation). She was initiated on hemodialysis due to lack of improvement in renal function. Urine culture done prior to initiation of antibiotics was positive for , which was later confirmed by renal biopsy. Extensive workup for the cause of renal failure including for connective tissue disease, plasmacytoma, obstruction was negative. She was treated with 6 week course of antibiotics with eventual recovery of her renal function in 4 months.
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http://dx.doi.org/10.1136/bcr-2018-227996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389091PMC
February 2019

Donor APOL1 high-risk genotypes are associated with increased risk and inferior prognosis of de novo collapsing glomerulopathy in renal allografts.

Kidney Int 2018 12 2;94(6):1189-1198. Epub 2018 Oct 2.

Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA. Electronic address:

Collapsing focal segmental glomerulosclerosis (cFSGS) in the native kidney is associated with heavy proteinuria and accelerated renal failure. However, cFSGS in the renal allograft is less well characterized. Here we report clinico-pathologic features and APOL1 donor risk genotypes in 38 patients with de novo post-kidney transplant cFSGS. Recipients were 34% female and 26% African American. Concurrent viral infections and acute vaso-occlusion (including thrombotic microangiopathy, cortical necrosis, atheroembolization, and cardiac arrest with contralateral graft thrombosis) were present in 13% and 29% of recipients, respectively. Notably, 61% of patients had concurrent acute rejection and 47% received grafts from African American donors, of which 53% carried APOL1 high-risk genotypes. These frequencies of acute rejection and grafts from African American donors were significantly higher than in our general transplant population (35% and 16%, respectively). Patients had a median serum creatinine of 5.4 mg/dl, urine protein/creatinine 3.5 g/g, and 18% had nephrotic syndrome. Graft failure occurred in 63% of patients at an average of eighteen months post-index biopsy. By univariate analysis, donor APOL1 high-risk genotypes, post-transplant time, nephrotic syndrome, and chronic histologic changes were associated with inferior graft survival while acute vaso-occlusion was associated with superior graft survival. Donor APOL1 high-risk genotypes independently predicted poor outcome. Compared to native kidney cFSGS, post-transplant cFSGS had more acute vaso-occlusion but less proteinuria. Thus, de novo cFSGS is associated with variable proteinuria and poor prognosis with potential predisposing factors of African American donor, acute rejection, viral infection and acute vaso-occlusion. Additionally, donor APOL1 high-risk genotypes are associated with higher incidence and worse graft survival.
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http://dx.doi.org/10.1016/j.kint.2018.06.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251748PMC
December 2018

Donor's APOL1 Risk Genotype and "Second Hits" Associated With De Novo Collapsing Glomerulopathy in Deceased Donor Kidney Transplant Recipients: A Report of 5 Cases.

Am J Kidney Dis 2019 01 25;73(1):134-139. Epub 2018 Jul 25.

Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY; Columbia University Renal Epidemiology (CURE) Group and Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY.

The presence of 2 APOL1 risk variants (G1/G1, G1/G2, or G2/G2) is an important predictor of focal segmental glomerulosclerosis (FSGS) and chronic kidney disease in individuals of African descent. Although recipient APOL1 genotype is not associated with allograft survival, kidneys from deceased African American donors with 2 APOL1 risk variants demonstrate shorter graft survival. We present a series of cases of presumed de novo collapsing FSGS in 5 transplanted kidneys from 3 deceased donors later identified as carrying 2 APOL1 risk alleles, including 2 recipients from the same donor whose kidneys were transplanted in 2 different institutions. Four of these recipients had viremia in the period preceding the diagnosis of collapsing FSGS. Cytomegalovirus and BK virus infection were present in 3 and 1 of our 5 cases, respectively, around the time that collapsing FSGS occurred. We discuss viral infections, including active cytomegalovirus infection, as possible "second hits" that may lead to glomerular injury and allograft failure in these recipients. Further studies to identify additional second hits are necessary to better understand the pathologic mechanisms of donor APOL1-associated kidney disease in the recipient.
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http://dx.doi.org/10.1053/j.ajkd.2018.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309648PMC
January 2019

The Banff Working Group Classification of Definitive Polyomavirus Nephropathy: Morphologic Definitions and Clinical Correlations.

J Am Soc Nephrol 2018 02 26;29(2):680-693. Epub 2017 Dec 26.

Department of Pathology, Weill Cornell Medicine, New York, New York.

Polyomavirus nephropathy (PVN) is a common viral infection of renal allografts, with biopsy-proven incidence of approximately 5%. A generally accepted morphologic classification of definitive PVN that groups histologic changes, reflects clinical presentation, and facilitates comparative outcome analyses is lacking. Here, we report a morphologic classification scheme for definitive PVN from the Banff Working Group on Polyomavirus Nephropathy, comprising nine transplant centers in the United States and Europe. This study represents the largest systematic analysis of definitive PVN undertaken thus far. In a retrospective fashion, clinical data were collected from 192 patients and correlated with morphologic findings from index biopsies at the time of initial PVN diagnosis. Histologic features were centrally scored according to Banff guidelines, including additional semiquantitative histologic assessment of intrarenal polyomavirus replication/load levels. In-depth statistical analyses, including mixed effects repeated measures models and logistic regression, revealed two independent histologic variables to be most significantly associated with clinical presentation: intrarenal polyomavirus load levels and Banff interstitial fibrosis ci scores. These two statistically determined histologic variables formed the basis for the definition of three PVN classes that correlated strongest with three clinical parameters: presentation at time of index biopsy, serum creatinine levels/renal function over 24 months of follow-up, and graft failure. The PVN classes 1-3 as described here can easily be recognized in routine renal biopsy specimens. We recommend using this morphologic PVN classification scheme for diagnostic communication, especially at the time of index diagnosis, and in scientific studies to improve comparative data analysis.
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http://dx.doi.org/10.1681/ASN.2017050477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5791071PMC
February 2018

Troponin testing in the primary care setting.

Aust Fam Physician 2017 Nov;46(11):823-826

Background: Chest pain is a common presenting complaint in general practice. Serum troponin testing is an important clinical tool to help identify patients who present with suspected acute coronary syndrome (ACS).

Objective: This article will discuss the role of troponin testing in the diagnosis of ACS, and the role of high-sensitive troponin, which is now in widespread use. The importance of clinical acumen in the interpretation of troponin testing and the pitfalls of troponin testing in the primary care setting will also be explored.

Discussion: Patients should be promptly referred to the hospital when there is a high clinical suspicion of ACS. This is to ensure early diagnosis, provide specialist care and minimise the risk of complications. For patients who present with suspected ACS, troponin testing in the community should not delay referral to the emergency department. Troponin testing has a limited role in the primary care setting, which will be discussed in this article.
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November 2017

Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction: The CAMERA-MRI Study.

J Am Coll Cardiol 2017 Oct 27;70(16):1949-1961. Epub 2017 Aug 27.

The Baker Heart & Diabetes Institute, Clinical Electrophysiology Research, Melbourne, Australia; The Heart Centre, The Alfred Hospital, Melbourne, Australia; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia. Electronic address:

Background: Atrial fibrillation (AF) and left ventricular systolic dysfunction (LVSD) frequently co-exist despite adequate rate control. Existing randomized studies of AF and LVSD of varying etiologies have reported modest benefits with a rhythm control strategy.

Objectives: The goal of this study was to determine whether catheter ablation (CA) for AF could improve LVSD compared with medical rate control (MRC) where the etiology of the LVSD was unexplained, apart from the presence of AF.

Methods: This multicenter, randomized clinical trial enrolled patients with persistent AF and idiopathic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤45%). After optimization of rate control, patients underwent cardiac magnetic resonance (CMR) to assess LVEF and late gadolinium enhancement, indicative of ventricular fibrosis, before randomization to either CA or ongoing MRC. CA included pulmonary vein isolation and posterior wall isolation. AF burden post-CA was assessed by using an implanted loop recorder, and adequacy of MRC was assessed by using serial Holter monitoring. The primary endpoint was change in LVEF on repeat CMR at 6 months.

Results: A total of 301 patients were screened; 68 patients were enrolled between November 2013 and October 2016 and randomized with 33 in each arm (accounting for 2 dropouts). The average AF burden post-CA was 1.6 ± 5.0% at 6 months. In the intention-to-treat analysis, absolute LVEF improved by 18 ± 13% in the CA group compared with 4.4 ± 13% in the MRC group (p < 0.0001) and normalized (LVEF ≥50%) in 58% versus 9% (p = 0.0002). In those undergoing CA, the absence of late gadolinium enhancement predicted greater improvements in absolute LVEF (10.7%; p = 0.0069) and normalization at 6 months (73% vs. 29%; p = 0.0093).

Conclusions: AF is an underappreciated reversible cause of LVSD in this population despite adequate rate control. The restoration of sinus rhythm with CA results in significant improvements in ventricular function, particularly in the absence of ventricular fibrosis on CMR. This outcome challenges the current treatment paradigm that rate control is the appropriate strategy in patients with AF and LVSD. (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction [CAMERA-MRI]; ACTRN12613000880741).
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http://dx.doi.org/10.1016/j.jacc.2017.08.041DOI Listing
October 2017

NSAID Use and Cardiovascular Disease - A Cautionary Tale.

Heart Lung Circ 2017 Aug 27;26(8):753-756. Epub 2017 May 27.

School of Medicine, University of Adelaide, Adelaide, SA, Australia; Heart Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia; Department of Cardiology, Central Adelaide Local Health Network, Adelaide, SA, Australia.

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http://dx.doi.org/10.1016/j.hlc.2017.05.122DOI Listing
August 2017

Successful percutaneous closure of an extremely large secundum atrial septal defect during pregnancy.

Cardiovasc Diagn Ther 2017 Jun;7(3):336-339

Monash Heart, Monash Health, Monash Medical Centre, Clayton, Australia.

Atrial septal defects (ASDs) are one of the most of the most common acyanotic congenital heart lesions. Awareness of potential clinical presentations and complications during pregnancy is essential for those managing these patients. We report successful percutaneous closure of an extremely large secundum ASD, using the largest available percutaneous ASD closure device in a 27-year-old pregnant female. Large ASDs may have their initial clinical presentation and diagnosis during pregnancy. If indicated, percutaneous closure can be performed safely. Only a very small number of cases have previously reported this being performed safely during pregnancy.
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http://dx.doi.org/10.21037/cdt.2016.10.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440271PMC
June 2017

ICD Implantation in Patients with Nonischemic Heart Failure.

N Engl J Med 2017 01;376(1):90-91

Royal Adelaide Hospital, Adelaide, SA, Australia

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http://dx.doi.org/10.1056/NEJMc1614441DOI Listing
January 2017

The evolving role of cardiac magnetic resonance imaging in the assessment of cardiovascular disease.

Aust Fam Physician 2016 Oct;45(10):761-764

Background: Imaging of the heart is important in the diagnosis and follow-up of a broad range of cardiac pathology. The authors discuss the growing role of cardiac magnetic resonance imaging (CMR) in cardiology practice and its relevance to primary healthcare.

Objective: In this article we discuss the advantages of CMR over other imaging modalities, and give a brief description of the common CMR techniques and cardiac pathologies where CMR is especially useful.

Discussion: CMR provides specific advantages over other cardiac imaging modalities when evaluating pathology in congenital heart disease, cardiac masses, cardiomyopathies, and in some aspects of ischaemic and valvular heart diseases. The strength of CMR in these pathologies includes its precise ana-tomical delineation of structures, characterisation of myocardial tissue, and accurate, reproducible measurements of blood volume and flow. CMR is used in inpatient and outpatient settings, and is available primarily in major hospitals.
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October 2016

Severe left ventricular hypertrophy and marked cardiac fibrosis in Danon disease.

Int J Cardiol 2016 Oct 1;221:14-6. Epub 2016 Jul 1.

Alfred Hospital and BakerIDI Heart and Diabetes Institute, Department of Cardiovascular Medicine, Australia.

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http://dx.doi.org/10.1016/j.ijcard.2016.06.311DOI Listing
October 2016

Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors.

Kidney Int 2016 09 7;90(3):638-47. Epub 2016 Jun 7.

Divison of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. Electronic address:

Immune checkpoint inhibitors (CPIs), monoclonal antibodies that target inhibitory receptors expressed on T cells, represent an emerging class of immunotherapy used in treating solid organ and hematologic malignancies. We describe the clinical and histologic features of 13 patients with CPI-induced acute kidney injury (AKI) who underwent kidney biopsy. Median time from initiation of a CPI to AKI was 91 (range, 21 to 245) days. Pyuria was present in 8 patients, and the median urine protein to creatinine ratio was 0.48 (range, 0.12 to 0.98) g/g. An extrarenal immune-related adverse event occurred prior to the onset of AKI in 7 patients. Median peak serum creatinine was 4.5 (interquartile range, 3.6-7.3) mg/dl with 4 patients requiring hemodialysis. The prevalent pathologic lesion was acute tubulointerstitial nephritis in 12 patients, with 3 having granulomatous features, and 1 thrombotic microangiopathy. Among the 12 patients with acute tubulointerstitial nephritis, 10 received treatment with glucocorticoids, resulting in complete or partial improvement in renal function in 2 and 7 patients, respectively. However, the 2 patients with acute tubulointerstitial nephritis not given glucocorticoids had no improvement in renal function. Thus, CPI-induced AKI is a new entity that presents with clinical and histologic features similar to other causes of drug-induced acute tubulointerstitial nephritis, though with a longer latency period. Glucocorticoids appear to be a potentially effective treatment strategy. Hence, AKI due to CPIs may be caused by a unique mechanism of action linked to reprogramming of the immune system, leading to loss of tolerance.
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http://dx.doi.org/10.1016/j.kint.2016.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4983464PMC
September 2016

An unusual cause of hypertension with hematuria and proteinuria: Answers.

Pediatr Nephrol 2016 12 15;31(12):2265-2270. Epub 2016 Mar 15.

Columbia University Medical Center, New York, NY, 10032, USA.

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http://dx.doi.org/10.1007/s00467-016-3348-yDOI Listing
December 2016

An unusual cause of hypertension with hematuria and proteinuria: Questions.

Pediatr Nephrol 2016 12 15;31(12):2263-2264. Epub 2016 Mar 15.

Renal Pathology Laboratory, Department of Pathology, Columbia University College of Physicians and Surgeons, 630 W 168th St, VC14-224, New York, NY, 10032, USA.

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http://dx.doi.org/10.1007/s00467-016-3344-2DOI Listing
December 2016

Cardiogenic shock secondary to methamphetamine induced cardiomyopathy requiring veno-arterial extra-corporeal membrane oxygenation.

Int J Cardiol 2016 Mar 9;207:134-5. Epub 2016 Jan 9.

Department of Cardiovascular Medicine, Alfred Hospital, and BakerIDI Heart and Diabetes Institute, Melbourne Australia.

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http://dx.doi.org/10.1016/j.ijcard.2016.01.077DOI Listing
March 2016

Successful Bridge to Orthotopic Cardiac Transplantation with Implantation of a HeartWare HVAD in Management of Systemic Right Ventricular Failure in a Patient with Transposition of the Great Arteries and Previous Atrial Switch Procedure.

Heart Lung Circ 2016 May 2;25(5):e69-71. Epub 2015 Dec 2.

Department of Advanced Heart Failure/Transplantation, The Alfred Hospital, Melbourne, Vic, Australia.

A clinical case is described of a patient with a history of dextro-transposition of the great arteries (d-TGA) and prior atrial switch procedure who developed significant pulmonary hypertension whilst awaiting orthotopic cardiac transplantation. The increase in his pulmonary pressures necessitated de-listing for cardiac transplantation. A strategy of ventricular assist device (VAD) placement was then employed which provided improvement in his systemic cardiac output with left atrial off-loading to provide pulmonary vascular remodelling and consequently reduction in pulmonary vascular resistance (PVR). He was supported for a period of 408 days prior to successful orthotopic cardiac transplantation. A small number of cases with this abnormality undergoing VAD implantation have been described. Mechanical circulatory support has an important role in some patients with congenital heart disease.
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http://dx.doi.org/10.1016/j.hlc.2015.11.006DOI Listing
May 2016

Light Chain Proximal Tubulopathy: Clinical and Pathologic Characteristics in the Modern Treatment Era.

J Am Soc Nephrol 2016 05 15;27(5):1555-65. Epub 2015 Sep 15.

Departments of Pathology and.

Light chain proximal tubulopathy (LCPT) is characterized by cytoplasmic inclusions of monoclonal LC within proximal tubular cells. The significance of crystalline versus noncrystalline LCPT and the effect of modern therapies are unknown. We reported the clinical-pathologic features of 40 crystalline and six noncrystalline LCPT patients diagnosed between 2000 and 2014. All crystalline LCPTs were κ-restricted and displayed acute tubular injury. One-third of noncrystalline LCPT patients displayed λ-restriction or acute tubular injury. Only crystalline LCPT frequently required antigen retrieval to demonstrate monoclonal LC by immunofluorescence. In five of 38 patients, crystals were not detectable by light microscopy, but they were visible by electron microscopy. Hematolymphoid neoplasms, known before biopsy in only 15% of patients, included 21 monoclonal gammopathies of renal significance; 15 multiple myelomas; seven smoldering multiple myelomas; and three other neoplasms. Biopsy indications included Fanconi syndrome (38%; all with crystalline LCPT), renal insufficiency (83%), and proteinuria (98%). Follow-up was available for 30 (75%) patients with crystalline LCPT and all six patients with noncrystalline LCPT, of whom 11 underwent stem cell transplant, 16 received chemotherapy only, and nine were untreated. Complete or very good partial hematologic remissions occurred in six of 22 treated crystalline LCPT patients. By multivariable analysis, the only independent predictor of final eGFR was initial eGFR, highlighting the importance of early detection. All patients with crystalline LCPT treated with stem cell transplant had stable or improved kidney function, indicating the effectiveness of aggressive therapy in selected patients.
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http://dx.doi.org/10.1681/ASN.2015020185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849818PMC
May 2016

Left Ventricular Assist Device (LVAD) as a Bridge to Recovery for Tachycardia-Mediated Cardiomyopathy.

J Card Surg 2015 Nov 8;30(11):871-3. Epub 2015 Sep 8.

Department of Cardiothoracic Surgery, The Alfred Hospital and Monash University, Melbourne, Australia.

A case is described of cardiogenic shock that occurred following use of sotalol in a patient with severe left ventricular dysfunction. The patient required left ventricular assist device (LVAD) placement with subsequent myocardial recovery to a degree that allowed eventual device removal following 140 days of support.
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http://dx.doi.org/10.1111/jocs.12632DOI Listing
November 2015

Morphologic variants of focal segmental glomerulosclerosis and their significance.

Adv Chronic Kidney Dis 2014 Sep;21(5):400-7

Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, NY. Electronic address:

Focal segmental glomerulosclerosis (FSGS) comprises a group of clinical-pathologic syndromes characterized by heavy proteinuria and segmental obliteration of glomerular capillaries by extracellular matrix. FSGS lesions display morphologic heterogeneity with respect to their relationship to the glomerular vascular and tubular poles, the presence of capillary collapse, and endocapillary and extracapillary hypercellularity. A working proposal, commonly referred to as the Columbia Classification, distinguishes 5 mutually exclusive morphologic variants: collapsing, tip, cellular, perihilar, and not otherwise specified (NOS), which can be applied to primary and secondary forms of FSGS. Several studies have documented significant differences in baseline clinical characteristics and outcomes between morphologic variants of primary FSGS, supporting that this classification may provide useful prognostic information. The association of certain variants with particular secondary causes of FSGS suggests pathogenetic relevance.
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http://dx.doi.org/10.1053/j.ackd.2014.02.010DOI Listing
September 2014

Prevalence of cancer in membranous nephropathy: a systematic review and meta-analysis of observational studies.

Am J Nephrol 2014 28;40(1):29-35. Epub 2014 Jun 28.

Department of Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, N.Y., USA.

Background: The association between membranous nephropathy (MN) and cancer has been well documented. However, the true prevalence and characteristics of cancer associated with MN have not been well described.

Methods: A systematic review and meta-analysis of cohort studies was conducted to summarize the prevalence of cancer-associated MN as well as patient characteristics and types of cancer in this population. We used a random-effects meta-analysis model to estimate the prevalence of cancer.

Results: We included 6 studies (n = 785). The estimated prevalence of cancer was 10.0% (95% CI, 6.1-14.6). The mean age of MN patients with cancer was 67 ± 7 years. The diagnosis of cancer preceded the diagnosis of MN in 20 ± 6.8%. Lung cancer was the most common type of tumor, accounting for 22 cases (26%), followed by prostate cancer (13 cases, 15%), hematologic malignancies (12 cases, 14%), colorectal cancer (9 cases, 11%), breast cancer (6 cases, 7%), and stomach and esophageal cancer (5 cases, 6%).

Conclusion: The estimated prevalence of cancer in patients with MN is 10% (95% CI, 6.1-14.6). The vast majority of tumors associated with MN are lung and prostate cancer. Hematologic malignancies should also be considered as one of the potential cancers associated with MN. Our study was based on a largely Caucasian population; therefore, the findings might not be applicable to other populations.
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http://dx.doi.org/10.1159/000364782DOI Listing
September 2015

IgA nephropathy with minimal change disease.

Clin J Am Soc Nephrol 2014 Jun 10;9(6):1033-9. Epub 2014 Apr 10.

Department of Pathology and Cell Biology, Division of Renal Pathology, and.

Background And Objectives: Patients with IgA nephropathy typically present with hematuria and subnephrotic proteinuria. Nephrotic syndrome is uncommon in IgA nephropathy, and when present, it is usually associated with severe histologic features, such as endocapillary proliferation, segmental sclerosis, and crescent formation. Rarely, patients with IgA nephropathy present with nephrotic syndrome and only mild mesangial disease. This study sought to better characterize these patients.

Design, Setting, Participants, & Measurements: A retrospective review of cases of IgA nephropathy diagnosed from 2004 to 2011 identified patients with nephrotic range proteinuria and histologically mild IgA nephropathy. Specifically, using the Oxford Classification of IgA Nephropathy, we identified cases that lacked endocapillary proliferation or segmental sclerosis.

Results: The cohort consisted of 17 patients, including 10 men and 15 adults. The median serum creatinine was 0.9 mg/dl (range=0.7-3.1), median 24-hour urine protein was 8.0 g/d (3.0-18.0 g), and 14 patients were fully nephrotic, whereas the remaining 3 patients fulfilled two of three criteria for nephrotic syndrome. Biopsies revealed IgA-dominant or codominant deposits accompanied by mesangial proliferation in 14 patients (82.4%). Electron microscopy showed mesangial deposits and extensive foot process effacement (median=90%). Initial treatment consisted of corticosteroids, although many patients required additional agents to maintain remission status. Over a median follow-up of 20 months (2.2-82 months), 14 patients experienced a complete response, and 3 patients showed a partial response, with a median response time of 2 months (0.5-27 months). At least one relapse of nephrotic syndrome occurred in nine patients (53%). All patients exhibited stable or improved renal function over the follow-up period.

Conclusions: The findings in this cohort and previous studies suggest that rare cases of mild IgA nephropathy with nephrotic range proteinuria exhibit a clinical presentation, biopsy findings, treatment response, and outcome more typical of IgA nephropathy with superimposed minimal change disease. This study favors the view that such cases represent a dual glomerulopathy.
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http://dx.doi.org/10.2215/CJN.11951113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046738PMC
June 2014