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1.
Am J Transplant ; 21(2): 751-765, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32654372

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 2 , Transplante de Rim , Adulto , Índice de Massa Corporal , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Masculino , Fatores de Risco , Transplantados
2.
Kidney Med ; 5(2): 100585, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36712315

RESUMO

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.

3.
Clin Transplant ; 25(5): 721-30, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-20964717

RESUMO

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.


Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Rejeição de Enxerto/etnologia , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto/fisiologia , Transplante de Rim/efeitos adversos , Transplante de Rim/etnologia , Adolescente , Adulto , Idoso , Função Retardada do Enxerto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
4.
Cell Metab ; 2(5): 309-19, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16271531

RESUMO

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.


Assuntos
Ceruloplasmina/genética , Ceruloplasmina/metabolismo , Ferro/metabolismo , Animais , Proteínas de Transporte de Cátions/metabolismo , Duodeno/citologia , Duodeno/metabolismo , Enterócitos/metabolismo , Homeostase , Humanos , Absorção Intestinal , Ferro/sangue , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mucosa/metabolismo , RNA Mensageiro/metabolismo , Baço/metabolismo , Estresse Fisiológico/metabolismo , Fatores de Tempo , Transferrina/metabolismo
5.
Kidney Int ; 75(10): 1079-87, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19212414

RESUMO

Due to the shortage of organs, living donor acceptance criteria are becoming less stringent. An accurate determination of the glomerular filtration rate (GFR) is critical in the evaluation of living kidney donors and a value exceeding 80 ml/min per 1.73 m(2) is usually considered suitable. To improve strategies for kidney donor screening, an understanding of factors that affect GFR is needed. Here we studied the relationships between donor GFR measured by (125)I-iothalamate clearances (mGFR) and age, gender, race, and decade of care in living kidney donors evaluated at the Cleveland Clinic from 1972 to 2005. We report the normal reference ranges for 1057 prospective donors (56% female, 11% African American). Females had slightly higher mGFR than males after adjustment for body surface area, but there were no differences due to race. The lower limit of normal for donors (5th percentile) was less than 80 ml/min per 1.73 m(2) for females over age 45 and for males over age 40. We found a significant doubling in the rate of GFR decline in donors over age 45 as compared to younger donors. The age of the donors and body mass index increased over time, but their mGFR, adjusted for body surface area, significantly declined by 1.49+/-0.61 ml/min per 1.73 m(2) per decade of testing. Our study shows that age and gender are important factors determining normal GFR in living kidney donors.


Assuntos
Taxa de Filtração Glomerular , Transplante de Rim/normas , Doadores Vivos , Adulto , Negro ou Afro-Americano , Fatores Etários , Feminino , Humanos , Doadores Vivos/provisão & distribuição , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores Sexuais , População Branca
6.
Transplantation ; 86(2): 223-30, 2008 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-18645483

RESUMO

BACKGROUND: Accurate determination of kidney function is critical in the evaluation of living kidney donors and higher donor glomerular filtration rate (GFR) is associated with better allograft outcomes. However, among transplant centers donor kidney function evaluation varies widely. METHODS: The performance of creatinine clearance (CrCl), Modification of Diet in Renal Disease (MDRD), the re-expressed MDRD equations with standardized creatinine, and the Cockcroft-Gault (CG) formula as compared with (125)I-iothalamate GFR (iGFR) was analyzed in 423 donors. All methods of GFR measurement were then evaluated for their association with graft function at 1 year. RESULTS: The MDRD and re-expressed MDRD equations underestimated iGFR whereas CG showed minimal bias (median difference=-11.0, -16.3, and -0.5 mL/min/1.73 m(2), respectively). CrCl overestimated iGFR (10 mL/min/1.73 m(2)). The MDRD, re-expressed MDRD, and CG formulas were more accurate (88%, 86%, and 88% of estimates within 30% of iGFR, respectively) than CrCl (80% within 30% of iGFR). Interestingly, low bias and high accuracy were achieved by averaging the MDRD estimation with the CrCl result; both methods available to the clinician in most transplant centers. We also showed that predonation GFR as measured by isotopic renal clearance or any of the creatinine-based estimation formulas may be associated with allograft function at 1 year, whereas the widely used CrCl was not. CONCLUSIONS: Variable performance was seen among different GFR estimations, with CrCl being the poorest. Recent recommendations to use the MDRD equation with standardized serum creatinine did not improve its performance. However, recognizing the limited availability of GFR laboratories, these methods are still clinically useful if used with caution and understanding their limitations.


Assuntos
Creatinina/sangue , Creatinina/urina , Taxa de Filtração Glomerular , Transplante de Rim/métodos , Adulto , Estudos de Coortes , Feminino , Humanos , Testes de Função Renal , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento
7.
Cleve Clin J Med ; 75(5): 353-6, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18556877

RESUMO

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.


Assuntos
Anemia/tratamento farmacológico , Eritropoese/efeitos dos fármacos , Eritropoetina/efeitos adversos , Hemoglobinas/análise , Falência Renal Crônica/tratamento farmacológico , Receptores da Eritropoetina/efeitos dos fármacos , Anemia/etiologia , Antineoplásicos/efeitos adversos , Eritropoetina/biossíntese , Eritropoetina/uso terapêutico , Humanos , Falência Renal Crônica/complicações , Neoplasias/tratamento farmacológico , Valores de Referência , Diálise Renal , Fatores de Risco , Estados Unidos , United States Food and Drug Administration
8.
Transplantation ; 83(5): 593-9, 2007 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-17353780

RESUMO

Living donor renal allograft survival is superior to that achieved from deceased donors, although graft outcome is suboptimal in some of these patients. In an effort to identify the subset of patients at high risk for poor outcomes we studied donor risk factors in 248 living kidney donor-recipient pairs. Unadjusted donor (125)I-iothalamate GFR (iGFR), donor age more than 45 years, donor total cholesterol level less than 200 mg/dL, and donor systolic blood pressure (SBP) less than 120 mm Hg were correlated with allograft estimated glomerular filtration rate (eGFR), and incidence of acute rejection (AR), delayed graft function and/or graft loss at 2 years posttransplantation. Donor iGFR less than 110 mL/min (slope=-7.40, P<0.01), donors more than 45 years (slope=-8.76, P<0.01), donor total cholesterol levels more than 200 mg/dL (slope=-10.03, P<0.01), and SBP more than 120 mm Hg (slope=-5.60, P=0.03) were associated with lower eGFR. By multivariable linear regression analysis these variables remained independently associated with lower eGFR, and poorer outcomes. The increasing number of donor factors (age, iGFR, cholesterol, and blood pressure) was directly associated with worse posttransplant eGFR (P<0.01). In conclusion, our data suggest that routine assessment of living donor parameters could supplement the consideration of recipient characteristics in predicting posttransplant risk of graft injury/dysfunction.


Assuntos
Transplante de Rim/fisiologia , Doadores Vivos/classificação , Resultado do Tratamento , Doença Aguda , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Pressão Sanguínea , Colesterol/sangue , Família , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/epidemiologia , Humanos , Transplante de Rim/mortalidade , Doadores Vivos/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Transplante Homólogo
9.
Clin Ther ; 29(9): 2010-21, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18035200

RESUMO

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.


Assuntos
Anemia/sangue , Anemia/tratamento farmacológico , Eritropoetina , Eritropoetina/análogos & derivados , Hematínicos , Hemoglobinas/análise , Nefropatias/sangue , Idoso , Anemia/etiologia , Doença Crônica , Estudos de Coortes , Darbepoetina alfa , Esquema de Medicação , Epoetina alfa , Eritropoetina/administração & dosagem , Eritropoetina/uso terapêutico , Feminino , Hematínicos/administração & dosagem , Hematínicos/uso terapêutico , Humanos , Nefropatias/complicações , Masculino , Proteínas Recombinantes , Estudos Retrospectivos
10.
Cleve Clin J Med ; 73(3): 289-97, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16548452

RESUMO

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.


Assuntos
Anemia/tratamento farmacológico , Eritropoetina/análogos & derivados , Eritropoetina/uso terapêutico , Hematínicos/uso terapêutico , Nefropatias/tratamento farmacológico , Anemia/etiologia , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/etiologia , Doença Crônica , Darbepoetina alfa , Epoetina alfa , Humanos , Ferro/metabolismo , Ferro/uso terapêutico , Nefropatias/complicações , Guias de Prática Clínica como Assunto , Proteínas Recombinantes , Diálise Renal
11.
Endocr Pract ; 9(4): 301-6, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14561575

RESUMO

OBJECTIVE: To describe an unusual case of development of diabetes mellitus (DM) several years after manifestation of diabetic nephropathy and to review the related literature. METHODS: We present a case report, including detailed laboratory and pathologic findings in a 51-year-old man who was diagnosed as having DM several years after presenting with diabetic nephropathy. The pertinent literature is also reviewed. RESULTS: A 51-year-old African American man presented with proteinuria of 4 g/24 h. Past medical history was significant for impaired glucose tolerance diagnosed 2 years previously. Subsequent follow-up demonstrated fasting blood glucose levels ranging from 108 to 123 mg/dL and glycated hemoglobin levels ranging from 5.3 to 5.8%. The patient also had chronic hepatitis C, hypertension, a history of intravenous drug abuse, and a family history of DM and hypertension. On examination of the patient, his blood pressure was 180/90 mm Hg. Funduscopy revealed mild diabetic retinopathy. Work-up was negative for glomerulonephritis, connective tissue disease, vasculitis, or multiple myeloma. Kidney biopsy revealed thickened glomerular basement membranes and diffuse glomeru-losclerosis, consistent with diabetic nephropathy. During follow-up, 9 years after presenting with proteinuria and 4 years after diagnosis of biopsy-proven diabetic nephropathy, the patient had a blood glucose level of 890 mg/dL and diabetic ketoacidosis. CONCLUSION: This case provides one explanation for the natural course of patients who present with "diabetic complications" but have no diabetes. Some of those patients may have "prediabetes" and may manifest with DM during follow-up. We also conclude that hyperglycemia is not the only important factor in the pathogenesis of diabetic nephropathy.


Assuntos
Diabetes Mellitus Tipo 2/patologia , Nefropatias Diabéticas/patologia , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/diagnóstico , Retinopatia Diabética/patologia , Hemoglobinas Glicadas/metabolismo , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Rim/patologia , Masculino , Pessoa de Meia-Idade
12.
Blood Cells Mol Dis ; 33(3): 346-55, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15528156

RESUMO

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.


Assuntos
Anemia Hipocrômica/genética , Ceruloplasmina/genética , Eritropoese/efeitos dos fármacos , Oxidantes/administração & dosagem , Fenil-Hidrazinas/administração & dosagem , Anemia Hipocrômica/sangue , Animais , Ceruloplasmina/administração & dosagem , Eritropoese/genética , Humanos , Ferro/administração & dosagem , Ferro/sangue , Camundongos , Camundongos Knockout , Reticulócitos/metabolismo , Transferrina/administração & dosagem
13.
J Am Acad Dermatol ; 49(3): 541-3, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12963928

RESUMO

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.


Assuntos
Acantose Nigricans/complicações , Adenocarcinoma/etiologia , Neoplasias do Endométrio/etiologia , Acantose Nigricans/patologia , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia por Agulha , Carboplatina/administração & dosagem , Quimioterapia Adjuvante , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Seguimentos , Humanos , Histerectomia/métodos , Imuno-Histoquímica , Paclitaxel/administração & dosagem , Medição de Risco , Resultado do Tratamento
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