Hamid Rabb

Johns Hopkins University, Baltimore, Maryland, United States

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Publications (209)1291.54 Total impact

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    ABSTRACT: Ischemia-reperfusion injury (IRI) is a major cause of AKI, and previous studies established important roles for conventional CD4(+) T cells, natural killer T cells, and CD4(+)CD25(+)FoxP3(+) Tregs in AKI pathogenesis. We recently identified CD4(-)CD8(-) (double-negative; DN) T cells as an important subset of αβ T cell receptor-positive cells residing in mouse kidney. However, little is known about the pathophysiologic functions of kidney DN T cells. In this study, we phenotypically and functionally characterized murine kidney DN T cells in the steady state and in response to IRI. Unlike CD4(+) and CD8(+) T cells, DN T cells in the steady state expressed high levels of CD69, CD28, and CD40L; differentially expressed IL-27 and IL-10 anti-inflammatory cytokines; spontaneously proliferated at a very high rate; and suppressed in vitro proliferation of activated CD4(+) T cells. Within the first 3-24 hours after IRI, kidney DN T cells expanded significantly and upregulated expression of IL-10. In adoptive transfer experiments, DN T cells significantly protected recipients from AKI by an IL-10-dependent mechanism. DN T cells also made up a large fraction of the T cell compartment in human kidneys. Our results indicate that DN T cells are an important subset of the resident αβ(+) T cell population in the mammalian kidney and are early responders to AKI that have anti-inflammatory properties. Copyright © 2015 by the American Society of Nephrology.
    Journal of the American Society of Nephrology 08/2015; DOI:10.1681/ASN.2014121214 · 9.34 Impact Factor
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    ABSTRACT: T lymphocytes are established mediators of ischemia reperfusion (IR)-induced AKI, but traditional immune principles do not explain their mechanism of early action in the absence of alloantigen. Nrf2 is a transcription factor that is crucial for cytoprotective gene expression and is generally thought to have a key role in dampening IR-induced AKI through protective effects on epithelial cells. We proposed an alternative hypothesis that augmentation of Nrf2 in T cells is essential to mitigate oxidative stress during IR-induced AKI. We therefore generated mice with genetically amplified levels of Nrf2 specifically in T cells and examined the effect on antioxidant gene expression, T cell activation, cytokine production, and IR-induced AKI. T cell-specific augmentation of Nrf2 significantly increased baseline antioxidant gene expression. These mice had a high frequency of intrarenal CD25(+)Foxp3(+) regulatory T cells and decreased frequencies of CD11b(+)CD11c(+) and F4/80(+) cells. Intracellular levels of TNF-α, IFN-γ, and IL-17 were significantly lower in CD4(+) T cells with high Nrf2 expression. Mice with increased T cell expression of Nrf2 were significantly protected from functional and histologic consequences of AKI. Furthermore, adoptive transfer of high-Nrf2 T cells protected wild-type mice from IR injury and significantly improved their survival. These data demonstrate that T cell-specific activation of Nrf2 protects from IR-induced AKI, revealing a novel mechanism of tissue protection during acute injury responses. Copyright © 2015 by the American Society of Nephrology.
    Journal of the American Society of Nephrology 08/2015; DOI:10.1681/ASN.2014100978 · 9.34 Impact Factor
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    ABSTRACT: There have been few prospective controlled studies of kidney donors. Understanding the pathophysiologic effects of kidney donation is important for judging donor safety and improving our understanding of the consequences of reduced kidney function in chronic kidney disease. Prospective, controlled, observational cohort study. 3-year follow-up of kidney donors and paired controls suitable for donation at their donor's center. Kidney donation. Medical history, vital signs, glomerular filtration rate, and other measurements at 6, 12, 24, and 36 months after donation. At 36 months, 182 of 203 (89.7%) original donors and 173 of 201 (86.1%) original controls continue to participate in follow-up visits. The linear slope of the glomerular filtration rate measured by plasma iohexol clearance declined 0.36±7.55mL/min per year in 194 controls, but increased 1.47±5.02mL/min per year in 198 donors (P=0.005) between 6 and 36 months. Blood pressure was not different between donors and controls at any visit, and at 36 months, all 24-hour ambulatory blood pressure parameters were similar in 126 controls and 135 donors (mean systolic blood pressure, 120.0±11.2 [SD] vs 120.7±9.7mmHg [P=0.6]; mean diastolic blood pressure, 73.4±7.0 vs 74.5±6.5mmHg [P=0.2]). Mean arterial pressure nocturnal dipping was manifest in 11.2% ± 6.6% of controls and 11.3% ± 6.1% of donors (P=0.9). Urinary protein-creatinine and albumin-creatinine ratios were not increased in donors compared with controls. From 6 to 36 months postdonation, serum parathyroid hormone, uric acid, homocysteine, and potassium levels were higher, whereas hemoglobin levels were lower, in donors compared with controls. Possible bias resulting from an inability to select controls screened to be as healthy as donors, short follow-up duration, and dropouts. Kidney donors manifest several of the findings of mild chronic kidney disease. However, at 36 months after donation, kidney function continues to improve in donors, whereas controls have expected age-related declines in function. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
    American Journal of Kidney Diseases 03/2015; 66(1). DOI:10.1053/j.ajkd.2015.01.019 · 5.90 Impact Factor
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    ABSTRACT: CD4(-)CD8(-)double negative (DN) αβ T cells are legitimate components of the normal immune system. However, they are poorly understood and largely ignored by immunologists because of their historical association with the lymphoproliferation that occurs in mice (lpr and gld) and humans (autoimmune lymphoproliferative syndromes patients) with impaired Fas-mediated apoptosis where they are considered abnormal T cells. We believe that the traditional view that DN T cells that cause lymphoproliferation (hereafter referred to as lpr DN T cells) are CD4 and CD8 T cells that lost their coreceptor, conceived more than two decades ago, is flawed and that conflating lpr DN T cells with DN T cells found in normal immune system (hereafter referred to as nDN T cells) is unnecessarily dampening interest of this potentially important cell type. To begin rectifying these misperceptions, we will revisit the traditional view of lpr DN T cells and show that it does not hold true in light of recent immunological advances. In lieu of it, we offer a new model proposing that Fas-mediated apoptosis actively removes normally existing DN T cells from the periphery and that impaired Fas-mediated apoptosis leads to accumulation of these cells rather than de novo generation of DN T cells from activated CD4 or CD8 T cells. By doing so, we hope to provoke a new discussion that may lead to a consensus about the origin of lpr DN T cells and regulation of their homeostasis by the Fas pathway and reignite wider interest in nDN T cells.Immunology and Cell Biology advance online publication, 25 November 2014; doi:10.1038/icb.2014.99.
    Immunology and Cell Biology 11/2014; 93(3). DOI:10.1038/icb.2014.99 · 4.15 Impact Factor
  • Hye Ryoun Jang · Hamid Rabb
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    ABSTRACT: Acute kidney injury (AKI) prolongs hospital stay and increases mortality in various clinical settings. Ischaemia-reperfusion injury (IRI), nephrotoxic agents and infection leading to sepsis are among the major causes of AKI. Inflammatory responses substantially contribute to the overall renal damage in AKI. Both innate and adaptive immune systems are involved in the inflammatory process occurring in post-ischaemic AKI. Proinflammatory damage-associated molecular patterns, hypoxia-inducible factors, adhesion molecules, dysfunction of the renal vascular endothelium, chemokines, cytokines and Toll-like receptors are involved in the activation and recruitment of immune cells into injured kidneys. Immune cells of both the innate and adaptive immune systems, such as neutrophils, dendritic cells, macrophages and lymphocytes contribute to the pathogenesis of renal injury after IRI, and some of their subpopulations also participate in the repair process. These immune cells are also involved in the pathogenesis of nephrotoxic AKI. Experimental studies of immune cells in AKI have resulted in improved understanding of the immune mechanisms underlying AKI and will be the foundation for development of novel diagnostic and therapeutic targets. This Review describes what is currently known about the function of the immune system in the pathogenesis and repair of ischaemic and nephrotoxic AKI.
    Nature Reviews Nephrology 10/2014; 11(2). DOI:10.1038/nrneph.2014.180 · 8.54 Impact Factor
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    Hee-Seong Jang · Hamid Rabb · Babu J Padanilam
    Journal of the American Society of Nephrology 09/2014; 26(4). DOI:10.1681/ASN.2014090848 · 9.34 Impact Factor
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    ABSTRACT: The pathophysiology of acute kidney injury (AKI) involves multiple and overlapping immunological, biochemical, and hemodynamic mechanisms that modulate the effects of both the initial insult and the subsequent repair. Limited but recent experimental data have revealed that the intestinal microbiota significantly affects outcomes in AKI. Additional evidence shows significant changes in the intestinal microbiota in chronic kidney disease patients and in experimental AKI. In this minireview, we discuss the current status of the effect of intestinal microbiota on kidney diseases, the immunomodulatory effects of intestinal microbiota, and the potential mechanisms by which microbiota can modify kidney diseases and vice versa. We also propose future studies to clarify the role of intestinal microbiota in kidney diseases and to explore how the modification of gut microbiota may be a potential therapeutic tool. © 2014 S. Karger AG, Basel.
    Nephron Clinical Practice 09/2014; 127(1-4):139-43. DOI:10.1159/000363209 · 1.40 Impact Factor
  • M N Martina · S Noel · S Bandapalle · A R A Hamad · Hamid Rabb
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    ABSTRACT: The immune system is among the key pathogenic factors in acute kidney injury (AKI). Various immune cells, including dendritic cells, natural killer T cells, T and B lymphocytes, neutrophils and macrophages are involved. Conventional CD4+ lymphocytes are well established to participate in early injury, and CD4+CD25+FoxP3 regulatory T cells are protective and can accelerate repair. A newly identified kidney T cell receptor + CD4-CD8- (double-negative) T cell has complex functions, including potentially anti-inflammatory roles in AKI. In this mini review, we summarize the data on the role of lymphocytes in AKI and set the stage for further mechanistic studies as well as interventions to improve outcomes. © 2014 S. Karger AG, Basel.
    Nephron Clinical Practice 09/2014; 127(1-4):51-5. DOI:10.1159/000363719 · 1.40 Impact Factor
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    ABSTRACT: Cardiorenal syndromes (CRS) have been recently classified into five distinct entities, each with different major pathophysiologic mechanisms. CRS type 1 most commonly occurs in the setting of acutely decompensated heart failure where approximately 25% of patients develop a rise in serum creatinine and a reduction of urine output after the first several doses of intravenous diuretics. Altered cardiac and renal hemodynamics are believed to be the most important determinants of CRS type 1. CRS type 2 is the hastened progression of chronic kidney disease (CKD) in the setting of chronic heart failure. Accelerated renal cell apoptosis and replacement fibrosis is considered to be the dominant mechanism. CRS type 3 is acutely decompensated heart failure after acute kidney injury from inflammatory, toxic, or ischemic insults. This syndrome is precipitated by salt and water overload, acute uremic myocyte dysfunction, and neurohormonal dysregulation. CRS type 4 is manifested by the acceleration of the progression of chronic heart failure in the setting of CKD. Cardiac myocyte dysfunction and fibrosis, so-called 'CKD cardiomyopathy', is believed to be the predominant pathophysiologic mechanism. Type 5 CRS is simultaneous acute cardiac and renal injury in the setting of an overwhelming systemic insult such as sepsis. In this scenario, the predominant pathophysiological disturbance is microcirculatory dysfunction as a result of acutely abnormal immune cell signaling, catecholamine cellular toxicity, and enzymatic activation which result in simultaneous organ injury often extending beyond both the heart and the kidneys. This paper will summarize these and other key findings from an international consensus conference on the spectrum of pathophysiologic mechanisms at work in the CRS. © 2013 S. Karger AG, Basel.
    Blood Purification 07/2014; 37 Suppl 2(Suppl. 2):2-13. DOI:10.1159/000361059 · 1.28 Impact Factor
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    ABSTRACT: Background Although several strategies for treating early antibody-mediated rejection (AMR) in kidney transplants have been investigated, evidence on treatment of late AMR manifesting after 6 months is sparse. In this single-center series, we present data on 23 consecutive patients treated for late AMR. Methods Late AMR was diagnosed using Banff 2007 criteria along with presence of donor-specific antibodies (DSA) and acute rise in serum creatinine (SCr). Response to therapy was assessed by improvement in SCr, histologic improvement, and decline in DSA strength. Results Overall, 17% (4/23) had documented nonadherence while 69% (16/23) had physician-recommended reduction in immunosuppression before AMR. Eighteen patients (78%) were treated with plasmapheresis or low-dose IVIg+rituximab; 11 (49%) with refractory AMR also received one to three cycles of bortezomib. While there was an improvement (P=0.02) in mean SCr (2.4 mg/dL) at the end of therapy compared with SCr at the time of diagnosis (2.9 mg/dL), this improvement was not sustained at most recent follow-up. Eleven (48%) patients had no histologic resolution on follow-up biopsy. Lack of histologic response was associated with older patients (odds ratio [OR]=3.17; P=0.04), presence of cytotoxic DSA at time of diagnosis (OR=200; P=0.04), and severe chronic vasculopathy (cv2) on index biopsy (OR=50; P=0.06). Conclusions A major setting in which late AMR occurred in our cohort was reduction or change in immunosuppression. Our data demonstrate an inadequate response of late AMR to current and novel (bortezomib) therapies. The benefits of therapy need to be counterweighed with potential adverse effects especially in older patients, large antibody loads, and chronic allograft vasculopathy.
    Transplantation 06/2014; 97(12):1240-1246. DOI:10.1097/01.TP.0000442503.85766.91 · 3.83 Impact Factor
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    ABSTRACT: There is currently no standard protocol for the isolation of DN T cells from the non-lymphoid tissues despite their increasingly reported involvement in various immune responses. DN T cells are a unique immune cell type that has been implicated in regulating immune and autoimmune responses and tolerance to allotransplants(1-6). DN T cells are, however, rare in peripheral blood and secondary lymphoid organs (spleen and lymph nodes), but are major residents of the normal kidney. Very little is known about their pathophysiologic function(7) due to their paucity in the periphery. We recently described a comprehensive phenotypic and functional analysis of this population in the kidney(8) in steady state and during ischemia reperfusion injury. Analysis of DN T cell function will be greatly enhanced by developing a protocol for their isolation from the kidney. Here, we describe a novel protocol that allows isolation of highly pure ab CD4+ CD8+ T cells and DN T cells from the murine kidney. Briefly, we digest kidney tissue using collagenase and isolate kidney mononuclear cells (KMNC) by density gradient. This is followed by two steps to enrich hematopoietic T cells from 3% to 70% from KMNC. The first step consists of a positive selection of hematopoietic cells using a CD45+ isolation kit. In the second step, DN T cells are negatively isolated by removal of non-desired cells using CD4, CD8, and MHC class II monoclonal antibodies and CD1d α-galcer tetramer. This strategy leads to a population of more than 90% pure DN T cells. Surface staining with the above mentioned antibodies followed by FACs analysis is used to confirm purity.
    Journal of Visualized Experiments 05/2014; DOI:10.3791/51192 · 1.33 Impact Factor
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    ABSTRACT: Although the United States possesses one of the most comprehensive transplant registries in the world, nationally representative data on how transplant care is structured and delivered is lacking. Therefore, we surveyed all 208 adult kidney transplant centers in the United States, excluding 37 pediatric and 58 inactive adult centers. Respondents were asked about the characteristics of their kidney transplant programs (25 items), the structure and process of care (18 items), coordination of care (10 items), and the characteristics of transplant physicians and surgeons (9 items).The survey was completed by directors of 156 transplant centers (75% response). The results demonstrated significant variation between centers in several domains. Sixty-five percent of transplant centers do not have a dedicated transplant pharmacist in outpatient care. Two thirds of transplant centers do not see the kidney transplant recipients at least monthly during the first year. Less than 30% of centers perform joint sit-down or walking rounds between nephrology and transplant surgery.There was significant variation in the structure and process of care in kidney transplantation. This implies variation in the use of resources at the transplant centers. This variation should be studied to determine best practices associated with optimal kidney allograft and patient survival.
    Transplantation 05/2014; 98(5). DOI:10.1097/TP.0000000000000094 · 3.83 Impact Factor
  • Rudolf Pullmann · Hamid Rabb
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    ABSTRACT: The post-transcriptional regulation of gene expression occurs through cis RNA regulatory elements by the action of trans factors, which are represented by non-coding RNAs (especially microRNAs) and the turnover and translation regulatory RNA binding-proteins (TTR-RBPs). These multifactorial proteins are a group of heterogeneous RBPs primarily implicated in controlling the decay and translation rates of target mRNAs. TTR-RBPs usually shuttle between cellular compartments (nucleus, cytoplasm) in response to various stimuli and undergo post-translational modifications such as phosphorylation or methylation to ensure their proper subcellular localization and function. TTR-RBPs are emerging as key regulators of a wide variety of genes influencing kidney physiology and pathology. This review summarizes the current knowledge of TTR-RBPs that influence renal metabolism. We will discuss the role of TTR-RBPs as regulators of kidney ischemia, fibrosis and matrix remodeling, angiogenesis, membrane transport, immunity, vascular tone, hypertension, acid-base balance, as well as anemia, bone mineral disease, and vascular calcification.
    AJP Renal Physiology 01/2014; 306(6). DOI:10.1152/ajprenal.00270.2013 · 3.25 Impact Factor
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    ABSTRACT: Accumulated to-date microarray data on ischemia reperfusion injury (IRI) of kidney represent a powerful source for identifying new targets and mechanisms of kidney IRI. In this study, we conducted a meta-analysis of gene expression profiles of kidney IRI in human, pig, rat, and mouse models, using a new scoring method to correct for the bias of overrepresented species. The gene expression profiles were obtained from the public repositories for 24 different models. After filtering against inclusion criteria 21 experimental settings were selected for meta-analysis and were represented by 11 rat models, 6 mouse models, and 2 models each for pig and human, with a total of 150 samples. Meta-analysis was conducted using expression-based genome-wide association study (eGWAS). The eGWAS results were corrected for a rodent species bias using a new weighted scoring algorithm, which favors genes with unidirectional change in expression in all tested species. Our meta-analysis corrected for a species bias, identified 46 upregulated and 1 downregulated genes, of which 26 (55%) were known to be associated with kidney IRI or kidney transplantation, including LCN2, CCL2, CXCL1, HMOX1, ICAM1, ANXA1, and TIMP1, which justified our approach. Pathway analysis of our candidates identified "Acute renal failure panel" as the most implicated pathway, which further validates our new method. Among new IRI candidates were 10 novel (<5 published reports related to kidney IRI) and 11 new candidates (0 reports related to kidney IRI) including the most prominent candidates ANXA2, CLDN4, and TYROBP. The cross-species expression pattern of these genes allowed us to generate three workable hypotheses of kidney IRI, one of which was confirmed by an additional study. Our first in the field kidney IRI meta-analysis of 150 microarray samples, corrected for a species bias, identified 10 novel and 11 new candidate genes. Moreover, our new meta-analysis correction method improved gene candidate selection by identifying genes that are model and species independent, as a result, function of these genes can be directly extrapolated to the disease state in human and facilitate translation of potential diagnostic or therapeutic properties of these candidates to the bedside.
    BMC Nephrology 10/2013; 14(1):231. DOI:10.1186/1471-2369-14-231 · 1.69 Impact Factor
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    ABSTRACT: Acute kidney injury (AKI) caused by ischemia-reperfusion is a major clinical problem in both native and transplanted kidneys. We had previously shown that deficiency of Nrf2, a potent bZIP transcription factor that binds to the antioxidant response element, enhances susceptibility to experimental ischemic AKI. Here we further explored the role of Nrf2 in AKI by amplifying Nrf2 activation in vivo and in vitro with the synthetic triterpenoid CDDO-imidazolide. Mice treated with CDDO-imidazolide and undergoing experimental bilateral ischemic AKI had improved survival and renal function. Treated mice had improved renal histology with a decrease in tubular injury, as well as a decrease in proinflammatory cytokine and chemokine production compared with vehicle-treated mice. In an exploration of protective mechanisms, we found an upregulation of Nrf2 target antioxidant genes in CDDO-imidazolide-treated mouse kidneys. Furthermore, Nrf2-deficient mice treated with CDDO-imidazolide had no significant improvement in mortality, renal function or histology, proinflammatory cytokine gene expression, and no significant increase in antioxidant gene expression. In vitro studies demonstrated that the renal epithelial cells were likely an important target of CDDO-imidazolide. Thus, activation of Nrf2 signaling with CDDO-imidazolide confers protection from AKI, and presents a new therapeutic opportunity for this common and serious condition.Kidney International advance online publication, 2 October 2013; doi:10.1038/ki.2013.357.
    Kidney International 10/2013; 85(1). DOI:10.1038/ki.2013.357 · 8.56 Impact Factor
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    ABSTRACT: Focal segmental glomerulosclerosis (FSGS) recurs after kidney transplantation in more than 30% of cases and can lead to allograft loss. Serum soluble urokinase-type plasminogen activator receptor (suPAR) is implicated in the pathogenesis of native and recurrent FSGS. We conducted a retrospective study of 25 adults with posttransplantation FSGS. We investigated the relationship between suPAR levels and podocyte changes and the impact of therapy on podocyte structure. We assessed response to therapy by improvement in proteinuria, allograft function, and resolution of histologic changes. A median (interquartile range) of 15 (10-23) plasmapheresis sessions was administered; 13 of the subjects also received rituximab. Median pretreatment suPAR levels were higher among those with severe (≥75%) versus those with mild (≤25%) podocyte foot process effacement (13,030 vs. 4806 pg/mL; P=0.02). Overall, mean±SD of proteinuria improved from 5.1±3.8 to 2.1±2.8 mg/dL (P=0.003), mean podocyte effacement decreased from 57%±33% to 22%±22% (P=0.0001), estimated glomerular filtration rates increased from median (interquartile range) of 32.9 (20.6-44.2) to 39.3 (28.8-63.4; P<0.0001), and suPAR levels decreased from a median of 6.781 to 4.129 pg/mL (P=0.02) with therapy. Podocyte effacement is the first pathologic manifestation of FSGS after transplantation. The degree of podocyte effacement correlates with suPAR levels at time of diagnosis. Response to therapy results in significant reduction of suPAR levels and complete or significant improvement of podocyte effacement.
    Transplantation 07/2013; 96(7). DOI:10.1097/TP.0b013e31829eda4f · 3.83 Impact Factor
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    ABSTRACT: BACKGROUND: A comprehensive assessment of the association of patients' renal replacement therapy (RRT) modality with their participation in life activities (physical function, travel, recreation, freedom, and work) is needed. STUDY DESIGN: Systematic review of peer-reviewed published studies. SETTING & POPULATION: Adults undergoing RRT (hemodialysis, peritoneal dialysis, or transplantation). SELECTION CRITERIA FOR STUDIES: We searched PubMed, Cochrane Library, and EMBASE from January 1980 through April 2012 for English-language articles that compared participation in life activities among patients receiving: (1) hemodialysis compared with peritoneal dialysis, (2) hemodialysis compared with kidney transplantation, or (3) peritoneal dialysis compared with kidney transplantation. PREDICTOR: RRT modality. OUTCOMES: Reported rates of physical function, travel, recreation, freedom, and work-related activities by RRT modality. RESULTS: 46 studies (6 prospective cohort, 38 cross-sectional, and 2 pre-post transplantation) provided relevant comparisons of life participation activities among patients treated with hemodialysis, peritoneal dialysis, and kidney transplantation. Studies were conducted in 1985-2011 among diverse patient populations in 16 distinct locations. A majority of studies reported greater life participation rates for patients with kidney transplants compared with patients receiving either hemodialysis or peritoneal dialysis. In contrast, a majority of studies reported no differences in outcomes between patients receiving hemodialysis and patients receiving peritoneal dialysis. These results were consistent throughout the study period, across diverse populations, and among the subset of studies that performed appropriate adjustments for potential confounding factors. LIMITATIONS: Many studies included in the review had significant design weaknesses. CONCLUSIONS: Evidence suggests that patients with kidney transplants may experience better rates of life participation compared with patients receiving dialysis, whereas patients receiving hemodialysis and patients receiving peritoneal dialysis may experience similar rates of life participation. Rigorously performed studies are needed to better inform patients about the association of RRT with these important patient-reported outcomes.
    American Journal of Kidney Diseases 05/2013; 62(5). DOI:10.1053/j.ajkd.2013.03.022 · 5.90 Impact Factor
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    ABSTRACT: Cardiorenal syndrome type 5 (CRS-5) includes conditions where there is a simultaneous involvement of the heart and kidney from a systemic disorder. Given the wide spectrum of diseases that contribute to CRS-5, several pathophysiological mechanisms are invoked representing the response of the heart and kidney to the contributing disorder that is ongoing. The nature, duration and the underlying condition of the heart and kidney strongly influence the clinical course of CRS-5. In this paper we discuss the pathophysiology of CRS-5 in the setting of sepsis as a model system for CRS-5 providing a brief overview of strategies for monitoring and therapeutic intervention. We offer a framework for reference for considering other disorders leading to CRS-5 where the development of cardiac and renal dysfunction is more insidious.
    Contributions to nephrology 05/2013; 182:174-194. DOI:10.1159/000349970 · 1.80 Impact Factor
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    Jieun Oh · Hamid Rabb
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    ABSTRACT: Adiponectin (APN) is known as an anti-inflammatory adipokine in obesity and atherosclerosis. Jin et al. examine the effects of APN deficiency in renal ischemia/reperfusion injury (IRI) using APN knockout mice and demonstrate that APN deficiency protects mice from IRI. This newly described role for APN in acute kidney injury opens up the possibility of novel mechanistic and therapeutic strategies from the cross-fertilization of the fields of obesity and kidney diseases. Kidney International (2013) 83, 546-548. doi:10.1038/ki.2012.479
    Kidney International 04/2013; 83(4):546-8. DOI:10.1038/ki.2012.479 · 8.56 Impact Factor
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    ABSTRACT: BACKGROUND: Most previous studies of living kidney donors have been retrospective and have lacked suitable healthy controls. Needed are prospective controlled studies to better understand the effects of a mild reduction in kidney function from kidney donation in otherwise healthy individuals. STUDY DESIGN: Prospective, controlled, observational cohort study. SETTING & PARTICIPANTS: Consecutive patients approved for donation at 8 transplant centers in the United States were asked to participate. For every donor enrolled, an equally healthy control with 2 kidneys who theoretically would have been suitable to donate a kidney also was enrolled. PREDICTOR: Kidney donation. MEASUREMENTS: At baseline predonation and at 6 months after donation, medical history, vital signs, measured (iohexol) glomerular filtration rate, and other measurements were collected. There were 201 donors and 198 controls who completed both baseline and 6-month visits and form the basis of this report. RESULTS: Compared with controls, donors had 28% lower glomerular filtration rates at 6 months (94.6 ± 15.1 [SD] vs 67.6 ± 10.1 mL/min/1.73 m(2); P < 0.001), associated with 23% greater parathyroid hormone (42.8 ± 15.6 vs 52.7 ± 20.9 pg/mL; P < 0.001), 5.4% lower serum phosphate (3.5 ± 0.5 vs 3.3 ± 0.5 mg/dL; P < 0.001), 3.7% lower hemoglobin (13.6 ± 1.4 vs 13.1 ± 1.2 g/dL; P < 0.001), 8.2% greater uric acid (4.9 ± 1.2 vs 5.3 ± 1.1 mg/dL; P < 0.001), 24% greater homocysteine (1.2 ± 0.3 vs 1.5 ± 0.4 mg/L; P < 0.001), and 1.5% lower high-density lipoprotein cholesterol (54.9 ± 16.4 vs 54.1 ± 13.9 mg/dL; P = 0.03) levels. There were no differences in albumin-creatinine ratios (5.0 [IQR, 4.0-6.6] vs 5.0 [IQR, 3.3-5.4] mg/g; P = 0.5), office blood pressures, or glucose homeostasis. LIMITATIONS: Short duration of follow-up and possible bias resulting from an inability to screen controls with kidney and vascular imaging performed in donors. CONCLUSIONS: Kidney donors have some, but not all, abnormalities typically associated with mild chronic kidney disease 6 months after donation. Additional follow-up is warranted.
    American Journal of Kidney Diseases 03/2013; 62(3). DOI:10.1053/j.ajkd.2013.01.027 · 5.90 Impact Factor

Publication Stats

7k Citations
1,291.54 Total Impact Points


  • 2002–2015
    • Johns Hopkins University
      • • Department of Medicine
      • • Division of Nephrology
      Baltimore, Maryland, United States
    • University College Dublin
      Dublin, Leinster, Ireland
  • 2001–2014
    • Johns Hopkins Medicine
      • • Division of Nephrology
      • • Department of Medicine
      Baltimore, Maryland, United States
  • 2007
    • St Vincent's University Hospital
      Dublin, Leinster, Ireland
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2004
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      Torrance, California, United States
    • University of Cincinnati
      • Division of Nephrology & Hypertension
      Cincinnati, OH, United States
  • 2003
    • Showa University
      • Division of Nephrology
      Shinagawa, Tōkyō, Japan
    • Mater Misericordiae University Hospital
      Dublin, Leinster, Ireland
  • 1998–2001
    • Hennepin County Medical Center
      Minneapolis, Minnesota, United States
  • 2000
    • University of Minnesota Duluth
      • Medical School
      Duluth, Minnesota, United States
  • 1999
    • Jacksonville University
      Jacksonville, Florida, United States
  • 1996–1999
    • University of South Florida
      • Division of Nephrology and Hypertension
      Tampa, Florida, United States
  • 1993–1998
    • James A. Haley Veterans Hospital
      Tampa, Florida, United States