Thomas L Nickolas

Columbia University, New York, New York, United States

Are you Thomas L Nickolas?

Claim your profile

Publications (66)428.21 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Measurement of marrow fat (MF) is important to the study of bone fragility. We measured MF on iliac biopsies and by spine/hip magnetic resonance spectroscopy in the same subjects. Noninvasively assessed spine MF and histomorphometrically assessed MF correlated well. MF quantity and relationships with bone volume differed by measurement site. Excess marrow fat has been implicated in the pathogenesis of osteoporosis in several populations. In the bone marrow, adipocytes and osteoblasts share a common precursor and are reciprocally regulated. In addition, adipocytes may secrete toxic fatty acids and adipokines that adversely affect osteoblasts. Measurement of marrow fat is important to the study of mechanisms of bone fragility. Marrow fat can be quantified on bone biopsy samples by histomorphometry and noninvasively by proton magnetic resonance spectroscopy ((1)H-MRS). In this study, we evaluate relationships between marrow fat assessed using both methods in the same subjects for the first time. Sixteen premenopausal women, nine with idiopathic osteoporosis and seven normal controls, had marrow fat measured at the iliac crest by bone biopsy and at the lumbar spine (L3) and proximal femur by (1)H-MRS. At L3, fat fraction by (1)H-MRS correlated directly and significantly with marrow fat variables on iliac crest biopsies (r = 0.5-0.8). In contrast, there were no significant correlations between fat fraction at the femur and marrow fat on biopsies. Marrow fat quantity (%) was greater at the femur than at L3 and the iliac crest and correlated inversely with total hip and femoral neck BMD by DXA. In summary, measurement of marrow fat in transiliac crest biopsies correlates with marrow fat at the spine but not the proximal femur by (1)H-MRS. There were site-specific differences in marrow fat quantity and in the relationships between marrow fat and bone volume.
    Osteoporosis International 05/2015; DOI:10.1007/s00198-015-3161-7 · 4.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with type 2 diabetes (T2DM) are at increased risk of fracture. High prevalence of chronic kidney disease (CKD) in T2DM may contribute to bone fragility, but whether dynamic change in kidney function is associated with fracture risk is unclear. To evaluate the association of pre-randomization baseline estimated glomerular filtration (eGFR) and its change over time with subsequent fracture risk in the Bone substudy of Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial, we conducted an observational study of 2262 women and 4737 men with T2DM and with at least 2 eGFR values. During a mean follow-up of 4.40±1.54 years, 235 women and 223 men sustained a new non-vertebral fracture. In multivariable adjusted sex-specific models, pre-randomization baseline eGFR was not a significant predictor of fracture risk in either men or women. However, a steeper decline in eGFR was associated with greater risk of fracture in women (hazard ratio [HR] per standard deviation [SD] decrement in eGFR slope, 1.30; 95%CI 1.17-1.44) but not men (HR per SD decrement in eGFR slope, 0.97; 95%CI 0.82-1.13). Accounting for competing risks of death modestly attenuated the association in women (HR per SD decrement in eGFR slope, 1.19; 95%CI 1.04-1.37), with the relationship in men remaining non-significant (HR per SD decrement in eGFR slope, 0.96; 95%CI 0.77-1.18). Declining kidney function predicts fracture risk in women but not in men with T2DM. Future studies should investigate the mechanisms for these associations. Copyright © 2015. Published by Elsevier Inc.
    Bone 04/2015; 78. DOI:10.1016/j.bone.2015.04.037 · 4.46 Impact Factor
  • Sophie A Jamal, Thomas L Nickolas
    [Show abstract] [Hide abstract]
    ABSTRACT: Fractures are more common and are associated with greater morbidity and morality in patients with kidney disease than in members of the general population. Thus, it is troubling that in chronic kidney disease (CKD) patients there has been a paradoxical increase in fracture rates over the past 20 years compared to the general population. Increased fracture incidence in CKD patients may be driven in part by the lack of screening for fracture risk. In the general population, dual energy X-ray absorptiometry (DXA) is the clinical standard to stratify fracture risk, and its use has contributed to decreases in fracture incidence. In contrast, in CKD, fracture risk screening with DXA has been uncommon due to its unclear efficacy in predicting fracture and its inability to predict type of renal osteodystrophy. Recently, several prospective studies conducted in patients across the spectrum of kidney disease have demonstrated that bone mineral density measured by DXA predicts future fracture risk and that clinically relevant information regarding fracture risk is provided by application of the World Health Organization cutoffs for osteopenia and osteoporosis to DXA measures. Furthermore, novel high-resolution imaging tools, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), have been used to elucidate the effects of kidney disease on cortical and trabecular microarchitecture and bone strength and to identify potential targets for strategies that protect against fractures. This review will discuss the updated epidemiology of fractures in CKD, fracture risk screening by DXA, and the utility of state-of-the art imaging methods to uncover the effects of kidney disease on the skeleton.
    Current Osteoporosis Reports 03/2015; 13(3). DOI:10.1007/s11914-015-0262-3
  • Journal of Clinical Investigation 12/2014; 124(12):5521-5521. DOI:10.1172/JCI79744 · 13.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and objectives Various dietary strategies have been investigated to slow kidney function decline. However, it is unknown whether a Mediterranean diet, which has been associated with improved cardiovascular risk, is associated with change in kidney function. Design, setting, participants, & measurements This study used the Northern Manhattan Study, a prospective, multiethnic, observational cohort of participants who were stroke free at baseline. Data were collected between 1993 and 2008. Serum creatinirte measurements were taken a mean 6.9 years apart. A baseline dietary questionnaire was extrapolated into a previously used 9-point scoring system (MeDi). The primary outcome was incident eGFR<60 ml/min per 1.73 m(2)using the Modification of Diet in Renal Disease formula. A secondary outcome was the upper quartile of annualized eGFR decline (>= 2.5 ml/min per 1.73 m(2) per year). Conditional logistic regression models adjusted for demographics and baseline vascular risk factors. Results Mean baseline age was 64 years, with 59% women and 65% Hispanics (N=900); mean baseline eGFR was 83.1 ml/min per 1.73 m(2). Incident eGFR<60 ml/min per 1.73 m(2) developed in 14%. In adjusted models, every 1-point increase in the MeDi score, indicating increasing adherence to a Mediterranean diet, was associated with decreased odds of incident eGFR<60 ml/min per 1.73 m(2) (odds ratio, 0.83; 95% confidence interval, 0.71 to 0.96) and decreased odds of being in the upper quartile of eGFR decline (odds ratio, 0.88; 95% confidence interval, 0.79 to 0.98). Conclusions A Mediterranean diet was associated with a reduced incidence of eGFR<60 ml/min per 1.73 m(2) and upper quartile of eGFR decline in a multiethnic cohort.
    Clinical Journal of the American Society of Nephrology 10/2014; 9(11). DOI:10.2215/CJN.01080114 · 5.25 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hispanic Americans of Caribbean origin are a fast-growing subset of the US population, but there are no studies on bone density, microstructure and biomechanical integrity in this minority group. In this study, we aimed to compare Caucasian and Caribbean Hispanic postmenopausal American women with respect to these characteristics. Thirty-three Caribbean Hispanics were age-matched to thirty-three Caucasian postmenopausal women. At the lumbar spine, the Hispanic women had significantly lower areal bone mineral density (aBMD). At the radius by high-resolution peripheral quantitative computed tomography (HR-pQCT), there were minimal differences between Hispanic and Caucasian women. At the tibia, Hispanic women had lower trabecular volumetric bone density and trabecular number, and higher trabecular separation. Individual trabecula segmentation (ITS) analyses indicated that at the tibia, Hispanic women not only had significantly lower bone volume fraction, but also had significantly lower rod bone volume fraction, plate trabecular number, rod trabecular number and lower plate–plate, plate–rod and rod–rod junction densities compared to Caucasian women. The differences in bone quantity and quality contributed to lower whole bone stiffness at the radius, and both whole bone and trabecular bone stiffness at the tibia in Hispanic women. In conclusion, Hispanic women had poorer bone mechanical and microarchitectural properties than Caucasian women, especially at the load-bearing distal tibia.
    09/2014; 2:14016. DOI:10.1038/boneres.2014.16
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with chronic kidney disease (CKD) who undergo kidney transplantation experience bone loss and increased risk of fracture. However, the mechanisms of this bone loss are unclear. Our objective was to use image registration to define the cortex to assess changes in cortical porosity (Ct.Po) in patients undergoing first time kidney transplantation. We obtained serial measurements of parathyroid hormone (PTH) and bone turnover markers and used high-resolution peripheral quantitative computed tomography (HR-pQCT) to scan the distal radius and tibia in 31 patients (21 men, 10 women; age: 51.9 ± 13.4) at transplant and after 1 year. Baseline and 1 year images were aligned using a fully automated, intensity-based image registration framework. We compared three methods to define the cortical region of interest (ROI) and quantify the changes: 1) cortical bone was independently defined in baseline and follow-up scans; 2) cortical bone was defined as the common cortical ROI; and 3) the cortical ROI at baseline was carried forward to 1 year follow-up (baseline-indexed). By the independently defined ROI, Ct.Po increased 11.7% at the radius and 9.1% at the tibia, whereas by the common ROI, Ct.Po increased 14.6% at the radius and 9.1% at the tibia. By the baseline-indexed ROI, which provides insight into changes at the endocortical region, Ct.Po increased 63.4% at the radius and 17.6% at the tibia. We found significant relationships between changes in Ct.Po and bone formation and resorption markers at the radius. The strongest associations were found between markers and Ct.Po using the baseline-index method. We conclude that Ct.Po increases throughout the cortex after kidney transplant and this increase is particularly marked at the endocortical surface. These methods may prove useful for all HR-pQCT longitudinal studies, particularly when changes are expected at the endocortical region. © 2014 American Society for Bone and Mineral Research
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 09/2014; 30(3). DOI:10.1002/jbmr.2358 · 6.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bone mineralization density distribution (BMDD) is an important determinant of bone mechanical properties. The most available skeletal site for access to the BMDD is the iliac crest. Compared to cancellous bone much less information on BMDD is available for cortical bone. Hence, we analyzed complete transiliac crest bone biopsy samples from premenopausal women (n = 73) aged 25-48 years, clinically classified as healthy, by quantitative backscattered electron imaging for cortical (Ct.) and cancellous (Cn.) BMDD. The Ct.BMDD was characterized by the arithmetic mean of the BMDD of the cortical plates. We found correlations between Ct. and Cn. BMDD variables with correlation coefficients r between 0.42 and 0.73 (all p < 0.001). Additionally to this synchronous behavior of cortical and cancellous compartments, we found that the heterogeneity of mineralization densities (Ct.CaWidth), as well as the cortical porosity (Ct.Po) was larger for a lower average degree of mineralization (Ct.CaMean). Moreover, Ct.Po correlated negatively with the percentage of highly mineralized bone areas (Ct.CaHigh) and positively with the percentage of lowly mineralized bone areas (Ct.CaLow). In conclusion, the correlation of cortical with cancellous BMDD in the iliac crest of the study cohort suggests coordinated regulation of bone turnover between both bone compartments. Only in a few cases, there was a difference in the degree of mineralization of >1wt % between both cortices suggesting a possible modeling situation. This normative dataset of healthy premenopausal women will provide a reference standard by which disease- and treatment-specific effects can be assessed at the level of cortical bone BMDD.
    Calcified Tissue International 08/2014; 95(4). DOI:10.1007/s00223-014-9901-4 · 2.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The bone marrow niche is thought to act as a permissive microenvironment required for emergence or progression of hematological cancers. We hypothesized that osteoblasts, components of the niche involved in HSC function, influence the fate of leukemic blasts. We show that osteoblast numbers decrease by 55% in myelodysplasia and acute myeloid leukemia patients. Further, genetic depletion of osteoblasts in mouse models of acute leukemia increased circulating blasts and tumor engraftment in the marrow and spleen leading to higher tumor burden and shorter survival. Myelopoiesis increased and was coupled with a reduction in B-lymphopoiesis and compromised erythropoiesis suggesting that hematopoietic lineage/progression was altered. Treatment of mice with acute myeloid or lymphoblastic leukemia with a pharmacological inhibitor of the synthesis of duodenal serotonin, a hormone suppressing osteoblast numbers, inhibited loss of osteoblasts. Maintenance of the osteoblast pool restored normal marrow function, reduced tumor burden and prolonged survival. Leukemia prevention was due to maintenance of osteoblast numbers since inhibition of serotonin receptors alone in leukemic blasts did not affect leukemia progression. These results suggest that osteoblasts play a fundamental role in propagating leukemia in the marrow and may be a therapeutic target to induce hostility of the niche to leukemia blasts.
    Blood 08/2014; 124(18). DOI:10.1182/blood-2013-07-517219 · 10.43 Impact Factor
  • Thomas L Nickolas
    Clinical Journal of the American Society of Nephrology 06/2014; 9(7). DOI:10.2215/CJN.04660514 · 5.25 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Intercalated cells (A-ICs) within the collecting duct of the kidney are critical for acid-base homeostasis. Here, we have shown that A-ICs also serve as both sentinels and effectors in the defense against urinary infec-tions. In a murine urinary tract infection model, A-ICs bound uropathogenic E. coli and responded by acidify-ing the urine and secreting the bacteriostatic protein lipocalin 2 (LCN2; also known as NGAL). A-IC–depen-dent LCN2 secretion required TLR4, as mice expressing an LPS-insensitive form of TLR4 expressed reduced levels of LCN2. The presence of LCN2 in urine was both necessary and sufficient to control the urinary tract infection through iron sequestration, even in the harsh condition of urine acidification. In mice lacking A-ICs, both urinary LCN2 and urinary acidification were reduced, and consequently bacterial clearance was limited. Together these results indicate that A-ICs, which are known to regulate acid-base metabolism, are also critical for urinary defense against pathogenic bacteria. They respond to both cystitis and pyelonephritis by delivering bacteriostatic chemical agents to the lower urinary system.
    Journal of Clinical Investigation 06/2014; 124(7). DOI:10.1172/JCI71630 · 13.77 Impact Factor
  • Revekka Babayev, Thomas L Nickolas
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a complex disorder of bone and mineral metabolism that results in an excess risk of fractures, cardiovascular events and mortality. The management of the bone disorder aspect of CKD-MBD may require bone biopsy to determine appropriate treatment strategies. However, it is unclear when biopsy may be necessary and whether or not state-of-the art imaging and serologic testing can supplant the bone biopsy as a tool to assist with management decisions.
    Current Opinion in Nephrology and Hypertension 05/2014; DOI:10.1097/01.mnh.0000447014.36475.58 · 4.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The majority of fragility fractures occur in women with osteopenia rather than osteoporosis as determined by dual‐energy X‐ray absorptiometry (DXA). However, it is difficult to identify which women with osteopenia are at greatest risk. We performed this study to determine whether osteopenic women with and without fractures had differences in trabecular morphology and biomechanical properties of bone. We hypothesized that women with fractures would have fewer trabecular plates, less trabecular connectivity, and lower stiffness. We enrolled 117 postmenopausal women with osteopenia by DXA (mean age 66 years; 58 with fragility fractures and 59 nonfractured controls). All had areal bone mineral density (aBMD) measured by DXA. Trabecular and cortical volumetric bone mineral density (vBMD), trabecular microarchitecture, and cortical porosity were measured by high‐resolution peripheral computed tomography (HR‐pQCT) of the distal radius and tibia. HR‐pQCT scans were subjected to finite element analysis to estimate whole bone stiffness and individual trabecula segmentation (ITS) to evaluate trabecular type (as plate or rod), orientation, and connectivity.Groups had similar age, race, body mass index (BMI), and mean T‐scores. Fracture subjects had lower cortical and trabecular vBMD, thinner cortices, and thinner, more widely separated trabeculae. By ITS, fracture subjects had fewer trabecular plates, less axially aligned trabeculae, and less trabecular connectivity. Whole bone stiffness was lower in women with fractures. Cortical porosity did not differ. Differences in cortical bone were found at both sites, whereas trabecular differences were more pronounced at the radius.In summary, postmenopausal women with osteopenia and fractures had lower cortical and trabecular vBMD; thinner, more widely separated and rodlike trabecular structure; less trabecular connectivity; and lower whole bone stiffness compared with controls,despite similar aBMD by DXA. Our results suggest that in addition to trabecular and cortical bone loss, changes in plate and rod structure may be important mechanisms of fracture in postmenopausal women with osteopenia.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 05/2014; 29(5):1101-9. · 6.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The majority of fragility fractures occur in women with osteopenia rather than osteoporosis by dual energy x-ray absorptiometry (DXA). However, it is difficult to identify which women with osteopenia are at greatest risk. We performed this study to determine whether osteopenic women with and without fracture had differences in trabecular morphology and biomechanical properties of bone. We hypothesized that women with fractures would have fewer trabecular plates, less trabecular connectivity and lower stiffness. We enrolled 117 postmenopausal women with osteopenia by DXA (mean age 66 years; 58 with fragility fractures and 59 non-fractured controls). All had areal bone mineral density by DXA. Trabecular and cortical volumetric BMD (vBMD), trabecular microarchitecture, and cortical porosity were measured by high resolution peripheral computed tomography (HR-pQCT) of the distal radius and tibia. HR-pQCT scans were subjected to finite element analysis to estimate whole bone stiffness and individual trabecula segmentation (ITS) to evaluate trabecular type (as plate or rod), orientation and connectivity. Groups had similar age, race, BMI, and mean T-scores. Fracture subjects had lower cortical and trabecular vBMD, thinner cortices, and thinner more widely separated trabeculae. By ITS, fracture subjects had fewer trabecular plates, less axially aligned trabeculae and less trabecular connectivity. Whole bone stiffness was lower in women with fractures. Cortical porosity did not differ. Differences in cortical bone were found at both sites, whereas trabecular differences were more pronounced at the radius. In summary, postmenopausal women with osteopenia and fractures had lower cortical and trabecular vBMD, thinner, more widely separated and rod-like trabecular structure, less trabecular connectivity and lower whole bone stiffness compared to controls, despite similar aBMD by DXA. Our results suggest that in addition to trabecular and cortical bone loss, changes in plate and rod structure may be important mechanisms of fracture in postmenopausal women with osteopenia. © 2013 American Society for Bone and Mineral Research
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 05/2014; 29(5). DOI:10.1002/jbmr.2144 · 6.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Context: Current guidelines for parathyroidectomy in primary hyperparathyroidism (PHPT) include an estimated glomerular filtration rate (eGFR) <60ml/min/1.73m(2). While the biochemical abnormalities associated with PHPT could impair renal function, there are currently no data examining whether more severe hypercalcemia, hypercalciuria or nephrolithiasis are associated with chronic kidney disease (CKD) in PHPT. Objective: This cross-sectional study evaluated predictors of renal function in PHPT. Design: This is a case series of PHPT patients with (eGFR<60ml/min/1.73m(2)) and without (eGFR≥60ml/min/1.73m(2)) CKD. Settings and Participants: We studied 114 PHPT patients in a university hospital setting. Outcome Measures: We identified predictors of renal function using multiple linear regression. Results: eGFR was associated with age, hypertension, anti-hypertensive medication use, fasting glucose, and 25-hydroxyvitamin D. eGFR was positively rather than negatively associated with several PHPT disease severity indices including, history of nephrolithiasis, 24-hour urinary calcium excretion and 1,25-dihydroxyvitamin D, but not serum calcium or PTH levels. An eGFR<60ml/min/1.73m(2) was observed in 15% (n=17), all of whom had stage 3 CKD (eGFR 30-59ml/min/1.73m(2)). Those with CKD were older, had higher 25-hydroxyvitamin D levels, lower 1,25-dihydroxyvitamin D levels and were more likely to be hypertensive than those without CKD. There were no between-group (<60 vs. ≥60ml/min/1.73m(2)) differences in serum calcium, PTH, nephrolithiasis or meeting surgical criteria other than eGFR. Multiple linear regression indicated that age and DBP were negatively associated with eGFR, while serum calcium, kidney stones and alcohol use were positive predictors. Calculation of eGFR using either the Modification of Diet in Renal Disease (MDRD) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation yielded similar results. Conclusions: PHPT patients with stage 3 CKD do not have biochemical or clinical evidence of more severe hyperparathyroidism compared to those without CKD. Traditional risk factors, rather than clinical or biochemical indices of PHPT, are associated with lower eGFR in mild PHPT.
    The Journal of Clinical Endocrinology and Metabolism 02/2014; 99(5):jc20134192. DOI:10.1210/jc.2013-4192 · 6.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The use of early corticosteroid withdrawal (ECSW) protocols after kidney transplantation has become common, but the effects on fracture risk and bone quality are unclear. We enrolled 47 first-time adult transplant recipients managed with ECSW into a 1-year study to evaluate changes in bone mass, microarchitecture, biomechanical competence, and remodeling with dual energy x-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT), parathyroid hormone (PTH) levels, and bone turnover markers obtained at baseline and 3, 6, and 12 months post-transplantation. Compared with baseline, 12-month areal bone mineral density by DXA did not change significantly at the spine and hip, but it declined significantly at the 1/3 and ultradistal radii (2.2% and 2.9%, respectively; both P<0.001). HRpQCT of the distal radius revealed declines in cortical area, density, and thickness (3.9%, 2.1%, and 3.1%, respectively; all P<0.001), trabecular density (4.4%; P<0.001), and stiffness and failure load (3.1% and 3.5%, respectively; both P<0.05). Findings were similar at the tibia. Increasing severity of hyperparathyroidism was associated with increased cortical losses. However, loss of trabecular bone and bone strength were most severe at the lowest and highest PTH levels. In summary, ECSW was associated with preservation of bone mineral density at the central skeleton; however, it was also associated with progressive declines in cortical and trabecular bone density at the peripheral skeleton. Cortical decreases related directly to PTH levels, whereas the relationship between PTH and trabecular bone decreases was bimodal. Studies are needed to determine whether pharmacologic agents that suppress PTH will prevent cortical and trabecular losses and post-transplant fractures.
    Journal of the American Society of Nephrology 02/2014; 25(6). DOI:10.1681/ASN.2013080851 · 9.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Half of the recovered expanded criteria donor (ECD) kidneys are discarded in the United States. A new kidney allocation system offers kidneys at higher risk of discard, Kidney Donor Profile Index (KDPI) > 85%, to a wider geographic area to promote broader sharing and expedite utilization. Dual kidney transplantation (DKT) based on the KDPI is a potential option to streamline allocation of kidneys which otherwise would have been discarded. To assess the clinical utility of the KDPI in kidneys at higher risk of discard, we analyzed the OPTN/UNOS Registry that included the deceased donor kidneys recovered between 2002 and 2012. The primary outcomes were allograft survival, patient survival and discard rate based on different KDPI categories (<80%, 80-90% and >90%). Kidneys with KDPI > 90% were associated with increased odds of discard (OR = 1.99, 95% CI 1.74-2.29) compared to ones with KDPI < 80%. DKTs of KDPI > 90% were associated with lower overall allograft failure (HR = 0.74, 95% CI 0.62-0.89) and better patient survival (HR = 0.79, 95% CI 0.64-0.98) compared to single ECD kidneys with KDPI > 90%. Kidneys at higher risk of discard may be offered in the up-front allocation system as a DKT. Further modeling and simulation studies are required to determine a reasonable KDPI cutoff percentile.
    American Journal of Transplantation 02/2014; 14(2):404-15. DOI:10.1111/ajt.12553 · 6.19 Impact Factor
  • S A Jamal, S L West, T L Nickolas
    [Show abstract] [Hide abstract]
    ABSTRACT: We assessed the ability of the World Health Organization's fracture risk assessment tool (FRAX), bone mineral density (BMD), and age to discriminate fracture status in adults with pre-dialysis chronic kidney disease (CKD). In adults with CKD, FRAX was able to discriminate fracture status but performed no better than BMD alone. Patients with CKD are at increased risk for fracture but the best method to assess fracture risk is not known. We assessed the ability of the World Health Organization's FRAX, compared with BMD at the femoral neck (FN), and age to discriminate fracture status (prevalent clinical nonspine and/or morphometric vertebral) in men and women, 18 years and older with pre-dialysis CKD. Results are presented as area under receiver operator characteristic curves (AUC) with 95 % confidence intervals (CI). We enrolled 353 subjects; mean age was 65 ± 14 years; weight was 79 ± 18 kg, and estimated glomerular filtration rate was 28 ml/min/1.73 m(2). About one third of the subjects had a prevalent clinical nonspine and/or morphometric vertebral fracture. FRAX was able to discriminate among those with prevalent clinical nonspine fractures (AUC, 0.72; 95 % CI, 0.65-0.78), morphometric vertebral fractures (AUC, 0.66; 95 % CI, 0.59-0.73), and any fracture (AUC, 0.71; 95 % CI, 0.65-0.77). The discriminative ability of BMD at the FN alone was similar to FRAX for morphometric vertebral and any fractures; FRAX performed better than BMD for prevalent clinical nonspine fractures (AUC for BMD alone, 0.66; 95 % CI, 0.60-0.73). Compared to FRAX, the AUC for age alone was lower for all fracture types. Among men and women with CKD, FRAX is able to discriminate fracture status but performs no better than BMD alone.
    Osteoporosis International 10/2013; 25(1). DOI:10.1007/s00198-013-2524-1 · 4.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic kidney disease (CKD) patients may have high rates of bone loss and fractures, but microarchitectural and biochemical mechanisms of bone loss in CKD patients have not been fully described. In this longitudinal study of 53 patients with CKD Stages 2-5D, we used dual energy X-ray absorptiometry (DXA), high resolution peripheral quantitative computed tomography (HRpQCT) and biochemical markers of bone metabolism to elucidate effects of CKD on the skeleton. Median follow-up was 1.5 years (Range 0.9 to 4.3 years); bone changes were annualized and compared to baseline. By DXA, there were significant declines in areal bone mineral density (BMD) of the total hip and ultradistal radius: -1.3% (95% CI: -2.1 to -0.6) and -2.4% (95% CI: -4.0 to -0.9), respectively. By HRpQCT at the distal radius, there were significant declines in cortical area, density and thickness, and increases in porosity: -2.9% (95% CI -3.7 to -2.2), -1.3% (95% CI -1.6 to -0.6), -2.8% (95% CI -3.6 to -1.9), and +4.2% (95% CI 2.0 to 6.4) respectively. Radius trabecular area increased significantly: +0.4% (95% CI 0.2 to 0.6), without significant changes in trabecular density or microarchitecture. Elevated time-averaged levels of parathyroid hormone (PTH) and bone turnover markers predicted cortical deterioration. Higher levels of serum 25-hydroxyvitamin D predicted decreases in trabecular network heterogeneity. These data suggest that significant cortical loss occurs with CKD, which is mediated by hyperparathyroidism and elevated turnover. Future investigations are required to determine whether these cortical losses can be attenuated by treatments that reduce PTH levels and remodeling rates. © 2013 American Society for Bone and Mineral Research.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 08/2013; 28(8). DOI:10.1002/jbmr.1916 · 6.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Context:Premenopausal women with idiopathic osteoporosis (IOP) have abnormal cortical and trabecular bone microarchitecture.Objective:The purpose of this study was to test the hypotheses that teriparatide increases bone mineral density (BMD) and bone formation and improves trabecular microarchitecture and stiffness in women with IOP.Design:This was an open-label pilot study.Setting:The setting was a tertiary care referral center.Patients:Participants were 21 premenopausal women with unexplained fragility fractures or low BMD.Intervention:Teriparatide was administered at 20 μg daily for 18 to 24 months.Main Outcome Measures:The primary endpoint was within-subject percent change in lumbar spine BMD. Secondary endpoints included percent change in hip and forearm BMD, transiliac biopsy parameters (trabecular bone volume, microarchitecture, stiffness, and adipocytes), serum N-terminal propeptide of procollagen type 1 (P1NP), and C-telopeptide.Results:BMD increased at the spine (10.8 ± 8.3% [SD]), total hip (6.2 ± 5.6%), and femoral neck (7.6 ± 3.4%) (all P < .001). Serum P1NP doubled by 1 month, peaked at 6 months, and returned to baseline by 18 to 24 months. Transiliac biopsies demonstrated significant increases in cortical width and porosity and trabecular bone volume and number increased, mirrored by a 71% increase in trabecular bone stiffness (P < .02-.001). Adipocyte area, perimeter, and volume/marrow volume decreased, with no change in adipocyte number. Four women had no increase in BMD and a blunted, delayed increase in serum P1NP. Nonresponders had markedly lower baseline bone formation rate (0.002 ± 0.001 vs 0.011 ± 0.006 mm(2)/mm/y; P < .001) and higher serum IGF-1 (208 ± 54 vs 157± 44 ng/mL; P = .03).Conclusions:Teriparatide was associated with increased spine and hip BMD and improved trabecular microarchitecture and stiffness at the iliac crest in the majority of women with IOP.
    The Journal of Clinical Endocrinology and Metabolism 03/2013; 98(5). DOI:10.1210/jc.2013-1172 · 6.31 Impact Factor