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Article: Anemia in chronic kidney disease: causes, diagnosis, treatment.

Nurko, Saul

2006 Volume 73, Issue 3, Page(s) 289–297

Abstract: Most patients with chronic kidney disease eventually become anemic. We should view the management of anemia in these patients as part of the overall management of the many clinically relevant manifestations of chronic kidney disease. Erythropoiesis- ... ...

Abstract	Most patients with chronic kidney disease eventually become anemic. We should view the management of anemia in these patients as part of the overall management of the many clinically relevant manifestations of chronic kidney disease. Erythropoiesis-stimulating agents (ESAs) are safe and should be used, as treating anemia may forestall some of the target-organ damage of chronic kidney disease.
MeSH term(s)	Anemia/drug therapy ; Anemia/etiology ; Anemia, Iron-Deficiency/drug therapy ; Anemia, Iron-Deficiency/etiology ; Chronic Disease ; Darbepoetin alfa ; Epoetin Alfa ; Erythropoietin/analogs & derivatives ; Erythropoietin/therapeutic use ; Hematinics/therapeutic use ; Humans ; Iron/metabolism ; Iron/therapeutic use ; Kidney Diseases/complications ; Kidney Diseases/drug therapy ; Practice Guidelines as Topic ; Recombinant Proteins ; Renal Dialysis
Chemical Substances	Hematinics ; Recombinant Proteins ; Erythropoietin (11096-26-7) ; Darbepoetin alfa (15UQ94PT4P) ; Epoetin Alfa (64FS3BFH5W) ; Iron (E1UOL152H7)
Language	English
Publishing date	2006-02-23
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	639116-3
ISSN	0891-1150
ISSN	0891-1150
DOI	10.3949/ccjm.73.3.289
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Article ; Online: Effects of body mass index on kidney transplant outcomes are significantly modified by patient characteristics.

Schold, Jesse D / Augustine, Joshua J / Huml, Anne M / Fatica, Richard / Nurko, Saul / Wee, Alvin / Poggio, Emilio D

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

2020 Volume 21, Issue 2, Page(s) 751–765

Abstract: Body mass index (BMI) is a known risk factor associated with kidney transplant outcomes and is incorporated for determining transplant candidate eligibility. However, BMI is a coarse health measure and risks associated with BMI may vary by patient ... ...

Abstract	Body mass index (BMI) is a known risk factor associated with kidney transplant outcomes and is incorporated for determining transplant candidate eligibility. However, BMI is a coarse health measure and risks associated with BMI may vary by patient characteristics. We evaluated 296 807 adult (age > 17) solitary kidney transplant recipients from the Scientific Registry of Transplant Recipients (2000-2019). We examined effects of BMI using survival models and tested interactions with recipient characteristics. Overall, BMI demonstrated a "J-Shaped" risk profile with elevated risks for overall graft loss with low BMI and obesity. However, multivariable models indicated interactions between BMI with recipient age, diagnosis, gender, and race/ethnicity. Low BMI was relatively higher risk for older recipients (>60 years), people with type I diabetes, and males and demonstrated no additional risk among younger (18-39) and Hispanic recipients. High BMI was associated with elevated risk for Caucasians and attenuated risk among African Americans and people with type II diabetes. Effects of BMI had variable risks for mortality vs graft loss by recipient characteristics in competing risks models. The association of BMI with posttransplant outcomes is highly variable among kidney transplant recipients. Results are important considerations for personalized care and risk stratification. Findings suggest that transplant contraindications should not be based on absolute BMI thresholds but modified based on patient characteristics.
MeSH term(s)	Adult ; Body Mass Index ; Diabetes Mellitus, Type 2 ; Graft Rejection/etiology ; Graft Survival ; Humans ; Kidney Transplantation/adverse effects ; Male ; Risk Factors ; Transplant Recipients
Language	English
Publishing date	2020-08-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2060594-8
ISSN	1600-6143 ; 1600-6135
ISSN (online)	1600-6143
ISSN	1600-6135
DOI	10.1111/ajt.16196
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Article: Anemia of chronic kidney disease: when normalcy becomes undesirable.

Demirjian, Sevag G / Nurko, Saul

Cleveland Clinic journal of medicine

2008 Volume 75, Issue 5, Page(s) 353–356

Abstract: In patients with chronic kidney disease and renal failure, hemoglobin levels have been rising in parallel with more intensive use of erythropoiesis-stimulating agents (ESAs). However, several recent studies indicate that raising hemoglobin to normal ... ...

Abstract	In patients with chronic kidney disease and renal failure, hemoglobin levels have been rising in parallel with more intensive use of erythropoiesis-stimulating agents (ESAs). However, several recent studies indicate that raising hemoglobin to normal levels with ESAs can be too much of a good thing. Compared with partial correction, normalization of hemoglobin did not improve outcome, and it may have led to more frequent adverse events. The US Food and Drug Administration (FDA) now recommends a hemoglobin goal in the range of 10 to 12 g/dL.
MeSH term(s)	Anemia/drug therapy ; Anemia/etiology ; Antineoplastic Agents/adverse effects ; Erythropoiesis/drug effects ; Erythropoietin/adverse effects ; Erythropoietin/biosynthesis ; Erythropoietin/therapeutic use ; Hemoglobins/analysis ; Humans ; Kidney Failure, Chronic/complications ; Kidney Failure, Chronic/drug therapy ; Neoplasms/drug therapy ; Receptors, Erythropoietin/drug effects ; Reference Values ; Renal Dialysis ; Risk Factors ; United States ; United States Food and Drug Administration
Chemical Substances	Antineoplastic Agents ; Hemoglobins ; Receptors, Erythropoietin ; Erythropoietin (11096-26-7)
Language	English
Publishing date	2008-06-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	639116-3
ISSN	0891-1150
ISSN	0891-1150
DOI	10.3949/ccjm.75.5.353
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Article ; Online: Renal Genetics Clinic: 3-Year Experience in the Cleveland Clinic.

Tan, Xin Yee / Borden, Chloe / Roberts, Mary-Beth / Mazzola, Sarah / Tan, Queenie K-G / Fatica, Richard / Simon, James / Calle, Juan / Taliercio, Jonathan / Dell, Katherine / Provenzano, Laura Ferreira / Deitzer, Diana / Rincon-Choles, Hernan / Mehdi, Ali / Lioudis, Michael / Poggio, Emilio D / Nakhoul, Georges / Nurko, Saul / Ashour, Tarek /

Bou Matar, Raed N / Kwon, Charles / Stephany, Brian / Thomas, George / Cheng, Yu-Wei / Leingang, Deanna / Alsadah, Adnan / Maditz, Rhyan / Robert, Heyka / Vachhrajani, Tushar / Sedor, John / Gadegbeku, Crystal / Wang, Xiangling

Kidney medicine

2022 Volume 5, Issue 2, Page(s) 100585

Abstract: Rationale & objective: There has been an increasing demand for the expertise provided by a renal genetics clinic. Such programs are limited in the United States and typically operate in a genomics research setting. Here we report a 3-year, real-world, ... ...

Abstract	Rationale & objective: There has been an increasing demand for the expertise provided by a renal genetics clinic. Such programs are limited in the United States and typically operate in a genomics research setting. Here we report a 3-year, real-world, single-center renal genetics clinic experience. Study design: Retrospective cohort. Setting & participants: Outpatient cases referred to the renal genetics clinic of the Cleveland Clinic between January 2019 and March 2022 were reviewed. Analytical approach: Clinical and laboratory characteristics were analyzed. All genetic testing was performed in clinical labs. Results: 309 new patients referred from 15 specialties were evaluated, including 118 males and 191 females aged 35.1 ± 20.3 years. Glomerular diseases were the leading presentation followed by cystic kidney diseases, electrolyte disorders, congenital anomalies of kidneys and urinary tract, nephrolithiasis, and tubulointerstitial kidney diseases. Dysmorphic features were noted in 27 (8.7%) patients. Genetic testing was recommended in 292 (94.5%) patients including chromosomal microarray (8.9%), single-gene tests (19.5%), multigene panels (77.3%), and exome sequencing (17.5%). 80.5% of patients received insurance coverage for genetic testing. 45% (115/256) of patients had positive results, 25% (64/256) had variants of unknown significance, and 22.3% (57/256) had negative results. 43 distinct monogenic disorders were diagnosed. Family history of kidney disease was present in 52.8% of patients and associated with positive genetic findings (OR, 2.28; 95% CI, 1.40-3.74). 69% of patients with positive results received a new diagnosis and/or a change in the diagnosis. Among these, 39.7% (31/78) of patients received a significant change in disease management. Limitations: Retrospective and single-center study. Conclusions: The renal genetics clinic plays important roles in the diagnosis and management of patients with genetic kidney diseases. Multigene panels are the most frequently used testing modality with a high diagnostic yield. Family history of kidney disease is a strong indication for renal genetics clinic referral.
Language	English
Publishing date	2022-12-13
Publishing country	United States
Document type	Journal Article
ISSN	2590-0595
ISSN (online)	2590-0595
DOI	10.1016/j.xkme.2022.100585
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Article: Dosing intervals and hemoglobin control in patients with chronic kidney disease and anemia treated with epoetin alfa or darbepoetin alfa: a retrospective cohort study.

Nurko, Saul / Spirko, Rita / Law, Amy / Dennis, Vincent W

Clinical therapeutics

2007 Volume 29, Issue 9, Page(s) 2010–2021

Abstract: Background: Anemia is a common complication of chronic kidney disease (CKD). The approved dosing interval for currently available erythropoiesis-stimulating agents (ESAs) is 2 to 3 times weekly for epoetin alfa (EPO) and every 1 to 2 weeks for ... ...

Abstract	Background: Anemia is a common complication of chronic kidney disease (CKD). The approved dosing interval for currently available erythropoiesis-stimulating agents (ESAs) is 2 to 3 times weekly for epoetin alfa (EPO) and every 1 to 2 weeks for darbepoetin alfa (DARB). However, clinicians sometimes use less frequent dosing in the interest of convenience. Objectives: This study investigated patterns of actual ESA use (doses and dosing intervals) and hemoglo- bin (Hb) control in adult outpatients with CKD not requiring dialysis at the Cleveland Clinic Foundation anemia clinic. The distribution of and variability in Hb levels in these patients were also examined. Methods: The clinical charts and electronic records of adult outpatients with CKD who initiated ESA therapy before March 2005 were reviewed to identify the initial, dominant (used for the longest consecutive period), and final dosing intervals and mean weekly doses of EPO and DARB. Hb control was examined in terms of maximum deviations >12 g/dL and <11 g/dL, and the proportions of measurements outside these values. Results: The analysis included data from 111 outpatients (mean [SD] age, 65.9 [14.4] years; 53.2% male; 66.7% white, 29.7% black, 2.7% other, 0.9% unknown ethnicity). Twenty-one patients received EPO only, 74 received DARB only, and 16 switched ESAs. The mean duration of follow-up was 20.5 months. The most common initial dosing intervals were qwk for EPO (66.7%) and q2wk for DARB (90.5%). The dominant dosing intervals were q2wk in 61.9% of EPO patients and q3wk in 62.3% of DARB patients. However, 80.0% of those who received EPO q2wk and 63.2% of those who received DARB q3wk eventually returned to their initial dosing intervals. The largest proportions of Hb mea- surements <11 g/dL occurred at dominant dosing intervals of qwk for EPO and q2wk for DARB (both, 46.0%; 11 and 26 patients, respectively), whereas the largest proportions of measurements >12 g/dL occurred with EPO dosed at q2wk (44.0%; 5 patients) and DARB dosed at >q4wk (62.0%; 5 patients). Conclusions: The patterns of ESA usage in adult outpatients with CKD at this center indicated that clinicians extended dosing intervals beyond those in the approved prescribing information. However, variations in Hb concentrations occurred during maintenance therapy administered at extended dosing intervals, resulting in the resumption of shorter dosing intervals in the majority of patients.
MeSH term(s)	Aged ; Anemia/blood ; Anemia/drug therapy ; Anemia/etiology ; Chronic Disease ; Cohort Studies ; Darbepoetin alfa ; Drug Administration Schedule ; Epoetin Alfa ; Erythropoietin/administration & dosage ; Erythropoietin/analogs & derivatives ; Erythropoietin/therapeutic use ; Female ; Hematinics/administration & dosage ; Hematinics/therapeutic use ; Hemoglobins/analysis ; Humans ; Kidney Diseases/blood ; Kidney Diseases/complications ; Male ; Recombinant Proteins ; Retrospective Studies
Chemical Substances	Hematinics ; Hemoglobins ; Recombinant Proteins ; Erythropoietin (11096-26-7) ; Darbepoetin alfa (15UQ94PT4P) ; Epoetin Alfa (64FS3BFH5W)
Language	English
Publishing date	2007-09
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603113-4
ISSN	1879-114X ; 0149-2918
ISSN (online)	1879-114X
ISSN	0149-2918
DOI	10.1016/j.clinthera.2007.09.012
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Zs.A 1435: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: The relative risk of overall graft loss and acute rejection among African American renal transplant recipients is attenuated with advancing age.

Schold, Jesse D / Srinivas, Titte R / Braun, William E / Shoskes, Daniel A / Nurko, Saul / Poggio, Emilio D

Clinical transplantation

2011 Volume 25, Issue 5, Page(s) 721–730

Abstract: Background: Graft loss rates are elevated among African American (AA) kidney transplant recipients. This may be attributable to immunological responses, socioeconomic disparities, comorbid conditions and access to care, but it is unclear whether risks ... ...

Abstract	Background: Graft loss rates are elevated among African American (AA) kidney transplant recipients. This may be attributable to immunological responses, socioeconomic disparities, comorbid conditions and access to care, but it is unclear whether risks are uniform in the AA population. Methods: We utilized multivariable models with the national SRTR database for adult recipients transplanted from 2000 to 2009 (n = 112,120) to investigate whether risks of graft loss, death and acute rejection between AAs and Caucasians vary with age. Results: Relative to Caucasians, AA recipients had significantly higher risk of overall graft loss among patients aged 18-49 (AHR = 1.37, 95% CI 1.30-1.43) but comparable risk among patients aged >65 (AHR = 1.04, 95% CI 0.96-1.13). Among recipients aged 18-34, AAs had higher risk of acute rejection (AOR = 1.33, 95% CI 1.12-1.57) but similar likelihood among recipients aged >65 (AOR = 0.94, 95% CI 0.75-1.17). Differences between race groups, as well as the relatively higher risks among younger AAs, were most pronounced following one yr post-transplantation and diminished with presence of other risk factors. Conclusions: Elevated risks of overall graft loss and acute rejection are present among younger but not older AA kidney transplant recipients. These findings may have important implications for treatment decisions, follow-up protocols and designation of "high-risk" patients.
MeSH term(s)	Adolescent ; Adult ; African Americans/statistics & numerical data ; Aged ; Delayed Graft Function ; Female ; Follow-Up Studies ; Graft Rejection/ethnology ; Graft Rejection/etiology ; Graft Survival/physiology ; Humans ; Kidney Transplantation/adverse effects ; Kidney Transplantation/ethnology ; Male ; Middle Aged ; Prognosis ; Young Adult
Language	English
Publishing date	2011-09
Publishing country	Denmark
Document type	Comparative Study ; Journal Article
ZDB-ID	639001-8
ISSN	1399-0012 ; 0902-0063
ISSN (online)	1399-0012
ISSN	0902-0063
DOI	10.1111/j.1399-0012.2010.01343.x
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Article: Malignant acanthosis nigricans and endometrioid adenocarcinoma of the parametrium: the search for malignancy.

Longshore, Sharon J / Taylor, James S / Kennedy, Alexander / Nurko, Saul

Journal of the American Academy of Dermatology

2003 Volume 49, Issue 3, Page(s) 541–543

Abstract: Malignant acanthosis nigricans is recognized as a cutaneous sign of internal malignancy, usually an adenocarcinoma. Although cases of malignant acanthosis nigricans have been associated with cervical, ovarian, and endometrial neoplasms, we describe a ... ...

Abstract	Malignant acanthosis nigricans is recognized as a cutaneous sign of internal malignancy, usually an adenocarcinoma. Although cases of malignant acanthosis nigricans have been associated with cervical, ovarian, and endometrial neoplasms, we describe a case with a rarely if ever reported association, endometrioid adenocarcinoma of the parametrium.
MeSH term(s)	Acanthosis Nigricans/complications ; Acanthosis Nigricans/pathology ; Adenocarcinoma/etiology ; Adenocarcinoma/pathology ; Adenocarcinoma/therapy ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy, Needle ; Carboplatin/administration & dosage ; Chemotherapy, Adjuvant ; Endometrial Neoplasms/etiology ; Endometrial Neoplasms/pathology ; Endometrial Neoplasms/therapy ; Female ; Follow-Up Studies ; Humans ; Hysterectomy/methods ; Immunohistochemistry ; Paclitaxel/administration & dosage ; Risk Assessment ; Treatment Outcome
Chemical Substances	Carboplatin (BG3F62OND5) ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2003-08-20
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	603641-7
ISSN	1097-6787 ; 0190-9622
ISSN (online)	1097-6787
ISSN	0190-9622
DOI	10.1067/s0190-9622(03)00913-7
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Article: Anemia and impaired stress-induced erythropoiesis in aceruloplasminemic mice.

Cherukuri, Srujana / Tripoulas, Nicholas A / Nurko, Saul / Fox, Paul L

Blood cells, molecules & diseases

2004 Volume 33, Issue 3, Page(s) 346–355

Abstract: Ceruloplasmin (Cp) is an abundant, copper-containing plasma protein with an important role in iron homeostasis. Patients with hereditary Cp deficiency have iron deposits in liver and other organs, consistent with impaired iron flux. The mild anemia ... ...

Abstract	Ceruloplasmin (Cp) is an abundant, copper-containing plasma protein with an important role in iron homeostasis. Patients with hereditary Cp deficiency have iron deposits in liver and other organs, consistent with impaired iron flux. The mild anemia reported in some patients suggests a possible role for Cp in iron delivery to red cell precursors during erythropoiesis. To investigate this function of Cp, we determined the hematologic parameters in Cp-deficient mice under normal conditions and after erythropoiesis-inducing stress. Cp(-/-) mice have below normal hematocrit, red cell hemoglobin and volume, and serum iron. Red cell number and turnover and reticulocyte counts were identical in Cp(-/-) and Cp(+/+) mice. Thus, Cp(-/-) have mild microcytic, hypochromic anemia consistent with normal red cell formation but defective iron availability. Cp(-/-) and Cp(+/+) mice subjected to phenylhydrazine-induced hemolytic anemia exhibited identical decreases in hematologic parameters, but Cp(-/-) mice showed diminished recovery after removal of the stress. Administration of purified human Cp or iron-saturated transferrin to Cp(-/-) mice partially restored hemoglobin formation in reticulocytes. The mild anemia in Cp(-/-) mice and the diminished response to stress may reflect inefficient recycling of iron between the reticuloendothelial and erythropoietic systems. Our findings suggest a role for Cp in erythropoiesis by providing sufficient iron to the erythroid tissue and that the requirement for Cp is raised after erythropoietic stress.
MeSH term(s)	Anemia, Hypochromic/blood ; Anemia, Hypochromic/genetics ; Animals ; Ceruloplasmin/administration & dosage ; Ceruloplasmin/genetics ; Erythropoiesis/drug effects ; Erythropoiesis/genetics ; Humans ; Iron/administration & dosage ; Iron/blood ; Mice ; Mice, Knockout ; Oxidants/administration & dosage ; Phenylhydrazines/administration & dosage ; Reticulocytes/metabolism ; Transferrin/administration & dosage
Chemical Substances	Oxidants ; Phenylhydrazines ; Transferrin ; phenylhydrazine (064F424C9K) ; Iron (E1UOL152H7) ; Ceruloplasmin (EC 1.16.3.1)
Language	English
Publishing date	2004-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1237083-6
ISSN	1096-0961 ; 1079-9796
ISSN (online)	1096-0961
ISSN	1079-9796
DOI	10.1016/j.bcmd.2004.07.003
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Article: Body mass index influences palpability but not stage of breast cancer at diagnosis.

Chagpar, Anees B / McMasters, Kelly M / Saul, Jeremy / Nurko, Jacob / Martin, Robert C G / Scoggins, Charles R / Edwards, Michael J

The American surgeon

2007 Volume 73, Issue 6, Page(s) 555–60; discussion 560

Abstract: Body mass index (BMI) is associated with breast cancer risk, but its relationship with stage at diagnosis is unclear. BMI was calculated for patients in the North American Fareston and Tamoxifen Adjuvant trial, and was correlated with clinicopathologic ... ...

Abstract	Body mass index (BMI) is associated with breast cancer risk, but its relationship with stage at diagnosis is unclear. BMI was calculated for patients in the North American Fareston and Tamoxifen Adjuvant trial, and was correlated with clinicopathologic factors, including stage at diagnosis. One thousand eight hundred fourteen patients were enrolled in the North American Fareston and Tamoxifen Adjuvant study; height and weight were recorded in 1451 (80%) of them. The median BMI was 27.1 kg/m2 (range, 14.7-60.7). The median patient age was 68 years (range, 42-100); median tumor size was 1.3 cm (range, 0.1-14 cm). One thousand seven hundred ninety-three (99.0%) patients were estrogen receptor positive, and 1519 (84.7%) were progesterone receptor positive. There was no significant relationship between BMI (as a continuous variable) and nodal status (P = 0.469), tumor size (P = 0.497), American Joint Committee on Cancer stage (P = 0.167), grade (P = 0.675), histologic subtype (P = 0.179), or estrogen receptor status (P = 0.962). Patients with palpable tumors, however, had a lower BMI than those with nonpalpable tumors (median 26.4 kg/m2 vs 27.5 kg/m2, P < 0.001). Similar results were found when BMI was classified as a categorical variable (<25 vs 25-29.9 vs > or =30). Increased BMI does not lead to a worse stage at presentation. Obese patients, however, tend to have nonpalpable tumors. Mammography in this population is especially important.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/therapeutic use ; Body Height ; Body Mass Index ; Body Weight ; Breast Neoplasms/diagnosis ; Breast Neoplasms/pathology ; Carcinoma, Ductal, Breast/diagnosis ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Lobular/diagnosis ; Carcinoma, Lobular/pathology ; Chemotherapy, Adjuvant ; Cohort Studies ; Estrogen Antagonists/therapeutic use ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Obesity/physiopathology ; Palpation ; Prospective Studies ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Tamoxifen/therapeutic use
Chemical Substances	Antineoplastic Agents, Hormonal ; Estrogen Antagonists ; Receptors, Estrogen ; Receptors, Progesterone ; Tamoxifen (094ZI81Y45)
Language	English
Publishing date	2007-06
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Multicenter Study ; Randomized Controlled Trial
ZDB-ID	202465-2
ISSN	1555-9823 ; 0003-1348
ISSN (online)	1555-9823
ISSN	0003-1348
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Article: Unexpected role of ceruloplasmin in intestinal iron absorption.

Cherukuri, Srujana / Potla, Ramesh / Sarkar, Joydeep / Nurko, Saul / Harris, Z Leah / Fox, Paul L

Cell metabolism

2005 Volume 2, Issue 5, Page(s) 309–319

Abstract: Ferroxidases are essential for normal iron homeostasis in most organisms. The paralogous vertebrate ferroxidases ceruloplasmin (Cp) and hephaestin (Heph) are considered to have nonidentical functions in iron transport: plasma Cp drives iron transport ... ...

Abstract	Ferroxidases are essential for normal iron homeostasis in most organisms. The paralogous vertebrate ferroxidases ceruloplasmin (Cp) and hephaestin (Heph) are considered to have nonidentical functions in iron transport: plasma Cp drives iron transport from tissue stores while intestinal Heph facilitates iron absorption from the intestinal lumen. To clarify the function of Cp, we acutely bled Cp-/- mice to stress iron homeostasis pathways. Red cell hemoglobin recovery was defective in stressed Cp-/- mice, consistent with low iron availability. Contrary to expectations, iron was freely released from spleen and liver stores in Cp-/- mice, but intestinal iron absorption was markedly impaired. Phlebotomy of wild-type mice caused a striking shift of Cp from the duodenal epithelium to the underlying lamina propria, suggesting a critical function of Cp in basolateral iron transport. Regulated relocalization of intestinal Cp may represent a fail-safe mechanism in which Cp shares with Heph responsibility for iron absorption under stress.
MeSH term(s)	Animals ; Cation Transport Proteins/metabolism ; Ceruloplasmin/genetics ; Ceruloplasmin/metabolism ; Duodenum/cytology ; Duodenum/metabolism ; Enterocytes/metabolism ; Homeostasis ; Humans ; Intestinal Absorption ; Iron/blood ; Iron/metabolism ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mucous Membrane/metabolism ; RNA, Messenger/metabolism ; Spleen/metabolism ; Stress, Physiological/metabolism ; Time Factors ; Transferrin/metabolism
Chemical Substances	Cation Transport Proteins ; RNA, Messenger ; Transferrin ; metal transporting protein 1 ; Iron (E1UOL152H7) ; Ceruloplasmin (EC 1.16.3.1)
Language	English
Publishing date	2005-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2176834-1
ISSN	1932-7420 ; 1550-4131
ISSN (online)	1932-7420
ISSN	1550-4131
DOI	10.1016/j.cmet.2005.10.003
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