Secondary hyperparathyroidism (CKD-MBD) treatment and the risk of dementia.

BACKGROUND: Elevated parathyroid hormone (PTH) levels have been reported as a potential risk factor for cognitive impairment. Compared with the general population, older adults with end-stage renal disease (ESRD) who are frequently affected by secondary hyperparathyroidism (SHPT) are at increased risk of developing dementia. The main objective of our study was to evaluate if the risk of dementia in older (age ≥66 years) ESRD patients differed if they were treated for SHPT. METHODS: Using the United States Renal Data System and Medicare claims, we identified 189 433 older adults without a diagnosis of dementia, who initiated dialysis between 2006 and 2016. SHPT treatment was defined as the use of vitamin D analogs, phosphate binders, calcimimetics or parathyroidectomy. We quantified the association between treated SHPT and incident dementia during dialysis using a multivariable Cox proportional hazards model with inverse probability weighting, considering SHPT treatment as a time-varying exposure. RESULTS: Of 189 433 older ESRD adults, 92% had a claims diagnosis code of SHPT and 123 388 (65%) were treated for SHPT. The rate of incident dementia was 6 cases per 100 person-years among SHPT treated patients compared with 11 cases per 100 person-years among untreated patients. Compared with untreated SHPT patients, the risk of dementia was 42% lower [adjusted hazard ratio (aHR) = 0.58, 95% confidence interval (CI): 0.56-0.59] among SHPT treated patients. The magnitude of the beneficial effect of SHPT treatment differed by sex (Pinteraction = .02) and race (Pinteraction ≤ .01), with females (aHR = 0.56, 95% CI: 0.54-0.58) and those of Asian (aHR = 0.51, 95% CI: 0.46-0.57) or Black race (aHR = 0.51, 95% CI: 0.48-0.53) having a greatest reduction in dementia risk. CONCLUSION: Receiving treatment for SHPT was associated with a lower risk of incident dementia among older patients with ESRD. This work provides additional support for the treatment of SHPT in older ESRD patients.

A review and perspective on the assessment, management and prevention of fragility fractures in patients with osteoporosis and chronic kidney disease.

This article aims to review the methods used for the assessment of fracture risk and the use of osteoporosis medications for fracture prevention in the population with CKD, and highlights the difficulties faced by clinicians in the management of these patients and the latest recommendations and guidelines. Chronic kidney disease (CKD) and osteoporosis often co-exist in older adults, and they present a major healthcare challenge. CKD mineral and bone disorder (CKD-MBD) occurs as renal function declines and this syndrome affects most patients in CKD stages 4 and 5. The biochemical abnormalities of CKD-MBD, renal bone disease and risk factors associated with age-related bone loss and osteoporosis lead to a cumulative effect on fracture risk and mortality. There is a need for routine evaluation of fracture risk and fracture prevention in this population. Measurement of bone mineral density (BMD) and the use of the FRAX tool have predictive value for incident fractures in the general population and in CKD. This enables physicians to identify CKD patients most at risk of sustaining a fragility fracture and allows a more targeted approach to fracture prevention. Data analysis from the pivotal trials of therapeutic agents used in osteoporosis show that these drugs can be considered in mild and moderate CKD (stages 1-3 CKD). Off-label drug use in patients with CKD-MBD and more severe renal impairment (CKD stages 4 and 5) could offer significant benefits to sub-groups of patients when carefully tailored to each individual's bone turnover and calcium and phosphate balance. However, this requires a selective approach and treatment decisions based on inference from pathophysiology while we await further trials. Guidelines advocate the correction and/or reduction of the biochemical abnormalities of CKD-MBD before initiation of treatment with osteoporosis drugs and close monitoring during treatment.

Parathyroid hormone measurement in chronic kidney disease: Impact of inter-method variability on mineral bone disease assessment.

BACKGROUND: Parathyroid hormone (PTH) is measured routinely as part of Chronic Kidney Disease Bone and Mineral Disorders (CKD-MBD) assessment. Multiple PTH assays exist with known differences resulting in CKD-MBD guidelines recommending treatment based on assay-specific thresholds. The study objectives are to assess between manufacturer and within manufacturer variability of PTH assays and the impact of assay variability on the assessment of CKD-BMD using both vendor defined and empirically derived thresholds. METHODS: Data were collected from Ontario, Canada's Proficiency Testing Program (24 challenge vials, 115-133 laboratories all using secondary generation PTH assays. Mean PTH and precision by the coefficient of analytical variation (CVa) were calculated. For each vial, whether the manufacturer's mean value exceeded the vendor-defined and empirically-derived upper limit of normal (ULN) was recorded and the concordance between assays was determined. RESULTS: Across all laboratories, the mean PTH range was 12.0 ± 3.9 pmol/L and the mean CVa was 30%. The percent of vials with a mean PTH exceeding manufacturer's specific ULN varied substantially between manufacturers. Only 58% of vials had complete concordance as to whether mean PTH was above assay-specific ULNs. This increased to 83% using the empirically derived ULN. CONCLUSIONS: CKD-BMD assessment and management will depend on the PTH assay. The between-assay variability is reduced but not eliminated when empirically derived reference intervals are used. Improvements in PTH measurement are required in order to ensure consistent patient care.

Eficacia y seguridad de denosumab en los pacientes adultos con mieloma múltiple, enfermedad ósea y enfermedad renal crónica avanzada / Efficacy and safety of denosumab in adult patients with multiple myeloma, bone disease, and advanced chronic kidney disease

INTRODUCCIÓN: El presente dictamen expone la evaluación de la eficacia y seguridad de denosumab en comparación con pamidronato para el tratamiento de los pacientes adultos con mieloma múltiple (MM) que tienen enfermedad ósea y enfermedad renal crónica avanzada (i. e. estadio 4 o 5 -ERCA-). El mieloma múltiple (MM) es una neoplasia maligna de las células plasmáticas que se asocia frecuentemente a enfermedad ósea (hasta en un 90 % de casos al momento del diagnóstico). La enfermedad ósea se caracteriza por un desbalance entre la reabsorción y la remodelación ósea, y se manifiesta clínicamente mediante los denominados eventos óseos que incluyen, por ejemplo, fracturas patológicas, dolor óseo severo, compresión vertebral, etc. Asimismo, el MM está también altamente asociado a la enfermedad renal crónica (ERC, hasta un 60 % de casos la desarrollan), siendo que los estadios cuatro y cinco corresponden a la ERC avanzada (ERCA), definida como una tasa de filtrado glomerular (TFG) < 30 mL/min. El Petitorio Farmacológico de EsSalud cuenta con los bifosfonatos (e. g. pamidronato) para el tratamiento de los pacientes con MM y enfermedad ósea. No obstante, los bifosfonatos se excretan a través del riñón por lo que cuentan con advertencia de uso en los pacientes con insuficiencia renal. En ese sentido, a pesar de que la etiqueta de pamidronato no recomienda su uso en los pacientes que presentan insuficiencia renal grave (i. e. ERCA), las guías de práctica clínica (GPC) internacionales vienen recomendando su uso en los pacientes con MM que tienen enfermedad ósea y ERCA, bajo ciertos parámetros que incluyen un monitoreo estricto de la función renal. Así, considerando el riesgo de daño renal con pamidronato, los especialistas han sugerido la evaluación de uso de denosumab, bajo la hipótesis de que este medicamento tendría un mejor perfil de eficacia y seguridad que los bifosfonatos en los pacientes con MM que tienen enfermedad ósea y ERCA. METODOLOGÍA: Se llevó a cabo una búsqueda bibliográfica sistemática, exhaustiva y jerárquica de la literatura con respecto a la eficacia y seguridad de denosumab comparada con pamidronato, para el tratamiento de pacientes adultos con MM con enfermedad ósea y ERCA. La búsqueda se inició revisando la información sobre el uso del medicamento de acuerdo con entidades reguladoras como FDA, EMA, y DIGEMID en el Perú. Se realizó tanto una búsqueda sistemática en las principales bases de datos, tales como MEDLINE vía PubMed y en Cochrane Library. Asimismo, se realizó una búsqueda manual en las páginas web de grupos dedicados a la investigación y educación en salud que elaboran guías de práctica clínica: National Institute for Health and Care Excellence (NICE), Canadian Agency for Drugs and Technologies in Health (CADTH), Scottish Medicines Consortium (SMC), Haute Authorité de Santé (HAS), Institute for Quality and Efficiency in Health Care (IQWiG), Institute for Clinical and Economic Review (ICER), la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA), la Organización Mundial de la Salud (OMS), el Ministerio de Salud del Perú (MINSA) y el Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI). Además, se realizó una búsqueda de las guías de las principales sociedades o instituciones especializadas en cáncer, tales como el Instituto Nacional de Enfermedades Neoplásicas (INEN) del Perú, National Comprehensive Cancer Network (NCCN), la American Society of Clinical Oncology (ASCO), la American Cancer Society, la European Society for Medical Oncology (ESMO), International Myeloma Working Group (IMWG), American Society for Blood and Marrow Transplantation (ASBMT), European Society of Blood and Marrow Transplantation (ESBMT), y European Myeloma Network (EMN). Adicionalmente, se buscaron ensayos clínicos en desarrollo o que no hayan sido publicados aún en la página web www.clinicaltrials.gov que contengan estudios acerca de la tecnología evaluada y así disminuir el sesgo de publicación. Finalmente, se consideró extraer información con una estrategia de "bola de nieve" mediante la revisión de las listas de referencias de las revisiones sistemáticas, estudios primarios y revisiones narrativas seleccionadas que sean relevantes para responder a la pregunta PICO. RESULTADOS: De acuerdo con la pregunta PICO, se llevó a cabo una búsqueda sistemática de la evidencia científica relacionada al uso de denosumab, comparado con pamidronato, como tratamiento de pacientes adultos con MM con enfermedad ósea y ERCA. En la presente sinopsis se describe la evidencia disponible según el tipo de publicación, siguiendo lo indicado en los criterios de elegibilidad (GPC, ETS, RS, MA y ECA fase III). CONCLUSIONES: El presente dictamen preliminar tiene como objetivo la evaluación de la mejor evidencia disponible sobre la eficacia y seguridad de denosumab, comparado con pamidronato, en los pacientes con MM que tienen enfermedad ósea y ERCA. La búsqueda sistemática de la literatura llevada a cabo hasta febrero del 2020 identificó dos GPC, de NCCN y de ASCO, pero no se encontró ningún ECA que haya comparado denosumab vs. pamidronato en la población de interés del presente dictamen. Las GPC incluidas en el presente dictamen preliminar recomiendan el uso de denosumab y pamidronato en los pacientes de la población de la pregunta PICO, como consenso formal entre los panelistas. Además, sugieren que denosumab sería preferible en los pacientes con deterioro renal, basados en una comparación por subgrupos no preespecificados proveniente del ECA de Raje et al. (2018), un estudio que evaluó la eficacia y seguridad de denosumab comparado con zoledronato (un bifosfonato diferente al comparador de interés) en pacientes adultos con MM y enfermedad ósea que excluyó a la población de interés del presente dictamen (pacientes con MM que tienen enfermedad ósea y ERCA), por lo que dichas recomendaciones deben ser tomadas con precaución. Dado que no existe evidencia directa sobre la eficacia y seguridad comparativa de denosumab y pamidronato en la subpoblación de pacientes con ERCA, se utilizó evidencia indirecta proveniente de estudios observacionales que alertan sobre un alto riesgo de hipocalcemia severa (alrededor del 50 %) con denosumab en los pacientes con ERCA, mientras que sugieren que pamidronato contaría con un perfil de seguridad tolerable en los pacientes con ERCA. Con la evidencia científica disponible a la fecha, no ha sido posible determinar un beneficio neto con denosumab, respecto a pamidronato en la población de la pregunta PICO. Dicha evidencia también sugiere que pamidronato podría ser una alternativa válida en la población de interés del presente dictamen preliminar; siendo ampliamente recomendado en las GPC internacionales y herramientas de referencia clínica basada en la evidencia como UpToDate y DynaMed para los pacientes adultos con MM que tienen enfermedad ósea, y ERCA. En ese sentido no es posible justificar la financiación de denosumab, en lugar de pamidronato, considerando la gran diferencia de costos entre ambas alternativas (costo anual por paciente de S/ 20,709.00 vs. S/ 367.90), mientras que la evidencia científica disponible a la fecha muestra incertidumbre en relación al balance riesgo-beneficio en la población de la pregunta PICO. Asimismo, pamidronato se encuentra actualmente disponible en el Petitorio Farmacológico de EsSalud, cuenta con amplia experiencia de uso por parte de los especialistas de la institución. Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI no aprueba el uso de denosumab como tratamiento de los pacientes adultos con MM, enfermedad ósea y ERCA.

Adherence to Kidney Disease: Improving Global Outcomes Mineral and Bone Guidelines for Monitoring Biochemical Parameters.

BACKGROUND: Mineral and bone disorder (MBD) is common in patients with chronic kidney disease (CKD), and is associated with risk of fractures, cardiovascular disease, and death. Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend monitoring CKD-MBD biochemical markers, including parathyroid hormone (PTH), phosphorus, 25-hydroxyvitamin D (25D), calcium, and alkaline phosphatase (ALP), in patients with moderate-to-severe CKD. METHODS: To determine guideline adherence, we used administrative claims records from the 20% sample of Medicare beneficiaries with Parts A, B, and D coverage, 2007 to 2015, and identified cohorts of patients with nondialysis stage 3, 4, or 5 CKD. Testing for biochemical markers during follow-up was defined based on laboratory procedure codes. Baseline factors associated with laboratory testing were determined using logistic regression. All analyses were performed separately by CKD stage. RESULTS: A total of 640,946 stage 3, 136,278 stage 4, and 22,076 stage 5 CKD patients, 50.2-52.9% women, mean age 74.4-78.0 years, were followed for a mean of 2.5, 1.3, and 0.7 years respectively. The frequency of testing was low for PTH (35.2-48.2%), phosphorus (46.6-62.0%), and 25D (29.3-46.7%). Testing was somewhat higher for calcium (88.1-95.4%) and ALP (63.5-88.1%); most tests were features of larger panels (e.g., basic metabolic panel). Older age, most comorbid conditions, and lack of prior nephrology care were associated with lower likelihood of testing. CONCLUSIONS: In fee-for-service Medicare beneficiaries, laboratory testing for CKD-MBD biochemical markers appears to be suboptimal in relation to KDIGO guidelines. Competing priories, such as management of comorbid disease and preparation for renal replacement therapy, may distract from CKD-MBD monitoring.

Racial-ethnic differences in chronic kidney disease-mineral bone disorder in youth on dialysis.

BACKGROUND: Studies in healthy pediatric populations and adults treated with dialysis demonstrate higher parathyroid hormone (PTH) and lower 25-hydroxyvitamin D levels in African-Americans. Despite these findings, African-Americans on dialysis demonstrate greater bone strength and a decreased risk of fracture compared to the Caucasian dialysis population. The presence of such differences in children and young adult dialysis patients is unknown. METHODS: Differences in the markers of mineral and bone metabolism (MBM) were assessed in 661 incident dialysis patients (aged 1 month to < 21 years). Racial-ethnic differences in PTH, calcium, phosphate, and total alkaline phosphatase (AP) activity were analyzed over the first year of dialysis using multivariate linear mixed models. RESULTS: African-American race predicted 23% higher serum PTH (95% CI, 4.7-41.3%) when compared to Caucasian patients, while Hispanic ethnicity predicted 17.5% higher PTH (95% CI, 2.3-38%). Upon gender stratification, the differences in PTH were magnified in African-American and Hispanic females: 38% (95% CI, 14.8-69.8%) and 28.8% (95% CI, 4.7-54.9%) higher PTH compared to Caucasian females. Despite higher PTH values, African-American females persistently demonstrated up to 10.9% lower serum AP activity (95% CI, - 20.6-- 0.7%). CONCLUSIONS: There are racial-ethnic differences in the markers of MBM. Higher PTH is seen in African-American and Hispanic children and young adults on dialysis with a magnification of this difference amongst the female population. There is a need to consider how factors like race, ethnicity, and gender impact the goal-targeted treatment of MBM disorders.

Evaluation of renal osteodystrophy in the dental clinic by assessment of mandibular and phalangeal cortical indices.

OBJECTIVES: Secondary hyperparathyroidism (SHPT) is a disease that affects patients with chronic kidney disease, and is characterized by mineral disturbance and bone loss, known as renal osteodystrophy. The aim of this study was to assess the validity of using intraoral phosphor storage plates to take radiographs of the middle phalanges to evaluate bone loss resulting from SHPT during follow-up of these patients. METHODS: The sample consisted of 24 patients with chronic kidney disease, 12 with parathyroid hormone (PTH) levels ≥500 pg/ml, and 12 with PTH levels <500 pg/ml, who underwent hemodialysis weekly. For each patient, a panoramic radiograph and digital radiographs of the ring, index, and middle fingers of both hands were taken. The Mandibular Cortical Index (MCI) and the Trabecular Bone Pattern Index (TBP) were applied to the panoramic radiographs, while the Phalangeal Cortical Index (PCI) was applied to the digital radiographs of the phalanges. Three evaluators performed all analyses. RESULTS: Significant correlations were found between the PTH levels and the MCI (p = 0.023), the PCI (p = 0.039) and the TBP index (p = 0.032). These parameters were also significantly interrelated (MCI × PCI = 0.001; MCI × TBP = 0.004 and PCI × TBP = 0.009). The PCI was shown to have the highest correlation with PTH levels. CONCLUSION: In patients with chronic renal disease, it is clinically relevant to use panoramic and digital radiographs using intraoral storage plates to assess a number of quantitative parameters that can be linked to PTH levels.

Skeletal status assessment by quantitative ultrasound and bone densitometry in children with different renal conditions.

Two methods of skeletal status assessment-quantitative ultrasound (QUS) and densitometry (DXA)-were applied and compared in a group of children with different renal disorders. Skeletal assessments in children with different renal conditions should rather not be based on a single diagnostic tool. Lumbar spine DXA is very effective to reveal disturbances secondary to glucocorticoids, whereas total body DXA and QUS are both better in identification of disturbances related to decreased GFR. INTRODUCTION: The aim of the study was to evaluate the skeletal status in children in different stages of chronic kidney disease (CKD) or treated with glucocorticoids, using either densitometry (DXA) or quantitative ultrasound (QUS) methods. METHODS: Seventy-six subjects (27 girls/49 boys) at the mean age of 11.8 ± 4.0 years were enrolled to the reported study. They were divided into three subgroups: with normal glomerular filtration rate (GFR) but treated with glucocorticoids (GCs, n = 38), with decreased GFR (CKD 2-5, n = 26) and with normal GFR and without any bone-toxic treatment (CKD 1, n = 12). DXA scans were carried out at lumbar spine (LS) and at total body (TB), and quantitative ultrasound (QUS) imaging was done at hand phalanges. QUS results were compared to those obtained from 310 healthy matched controls. RESULTS: The average Z-score for LS-BMD and TB-BMD was below zero in all the study subgroups. Neither were there any significant differences in the mean Z-score for LS among the subgroups. The mean Z-score for TB was significantly the lowest in the CKD 2-5 subgroup. The percentage of subjects with TB Z-score ≤ - 2.0 was the highest in the CKD 2-5 subgroup (69.2%), whereas the percentage of subjects with LS Z-score ≤ - 2.0 was the highest in the GC subgroup (23.7%). QUS results in CKD 2-5 were significantly lower than those in the controls, whereas the results, obtained in GC and CKD 1 subgroups, were similar to those in healthy subjects. CONCLUSIONS: Skeletal status assessment in children and adolescents with different renal conditions should not be based on single diagnostic approach. DXA scanning, performed at lumbar spine, is potentially more appropriate to reveal disturbances secondary to long-term GC therapy, whereas TB-DXA is highly effective in the identification of skeletal disturbances related to decreased kidney function. QUS at hand phalanges seems to be a useful diagnostic means in CKD with diminished GFR but insufficient to detect GC-related disturbances.

[New scenarios in secondary hyperparathyroidism: etelcalcetide. Position paper of Nephrologists form Lombardy].

Bone mineral abnormalities (defined as Chronic Kidney Disease Mineral Bone Disorder; CKD-MBD) are prevalent and associated with a substantial risk burden and poor prognosis in CKD population. Several lines of evidence support the notion that a large proportion of patients receiving maintenance dialysis experience a suboptimal biochemical control of CKD-MBD. Although no study has ever demonstrated conclusively that CKD-MBD control is associated with improved survival, an expanding therapeutic armamentarium is available to correct bone mineral abnormalities. In this position paper of Lombardy Nephrologists, a summary of the state of art of CKD-MBD as well as a summary of the unmet clinical needs will be provided. Furthermore, this position paper will focus on the potential and drawbacks of a new injectable calcimimetic, etelcalcetide, a drug available in Italy since few months ago.

CKD-MBD management: what is the role of parathyroidectomy? Results from a nationwide survey in Italy.

We herein report on a nationwide survey conducted in Italy to investigate the use of parathyroidectomy (PTX). In spite of the availability of newer and more effective drugs to control chronic kidney disease mineral bone disorder (CKD-MBD) biochemical abnormalities, PTX still remains a resource for nephrologists to use. However, observational analyses suggest that in recent years there has been a constant decline in the number of patients undergoing PTX. The reasons are not clear, though the increasing age and number of comorbidities of dialysis patients may partly explain this trend. Poor adherence to guidelines and/or geographical as well as logistic factors may also contribute to the lower use of PTX. The working group on CKD-MBD of the Italian Society of Nephrology launched a nationwide survey to investigate clinical practice patterns for PTX in Italy and identify modifiable factors that may limit accessibility to surgery.

Advances in the evaluation of bone health in kidney transplant patients. / Avances en la valoración de la salud ósea en el trasplantado renal.

Bone disease related to chronic kidney disease and, particularly, to kidney transplant patients is a common cause or morbidity and mortality, especially due to a higher risk of osteoporotic fractures. Despite the fact that this has been known for decades, to date, an appropriate diagnostic strategy has yet to be established. Apart from bone biopsy, which is invasive and scarcely used, no other technique is available to accurately establish the risk of fracture in kidney patients. Techniques applied to the general population, such as bone densitometry, have not been subjected to sufficient external validation and their use is not systematic. This means that the identification of patients at risk of fracture and therefore those who are candidates for preventive strategies is an unmet need. Bone strength, defined as the ability of the bone to resist fracture, is determined by bone mineral density (measured by bone densitometry), trabecular architecture and bone tissue quality. The trabecular bone score estimates bone microarchitecture, and low values have been described as an independent predictor of increased fracture risk. Bone microindentation is a minimally invasive technique that measures resistance of the bone to micro-cracks (microscopic separation of mineralised collagen fibres), and therefore bone tissue biomechanical properties. The superiority over bone densitometry of the correlation between the parameters measured by trabecular bone score and microindentation with the risk of fracture in diverse populations led us to test its feasibility in chronic kidney disease and kidney transplant patients.

Cost-effectiveness of dedicated dietitians for hyperphosphatemia management among hemodialysis patients in Lebanon: results from the Nutrition Education for Management of Osteodystrophy trial.

AIM: To assess the cost-effectiveness of nutrition education by dedicated dietitians (DD) for hyperphosphatemia management among hemodialysis patients. MATERIALS AND METHODS: This was a trial-based economic evaluation in 12 Lebanese hospital-based units. In total, 545 prevalent patients were cluster randomized to DD, trained hospital dietitian (THD), and existing practice (EP) groups. During Phase I (6 months), DD (n = 116) received intensive education by DD trained on renal nutrition, THD (n = 299) received care from trained hospital dietitians, and EP (n = 130) received usual care from untrained hospital dietitians. Patients were followed-up during Phase II (6 months). RESULTS: At baseline, EP had the lowest weekly hemodialysis time, and DD had the highest serum phosphorus and malnutrition-inflammation score. The additional costs of the intervention were low compared with the societal costs (DD: $76.7, $21,007.7; EP: $4.6, $18,675.4; THD: $17.4, $20,078.6, respectively). Between Phases I and II, DD showed the greatest decline in services use and societal costs (DD: -$2,364.0; EP: -$1,727.7; THD: -$1,105.7). At endline, DD experienced the highest decrease in adjusted serum phosphorus (DD: -0.32; EP: +0.16; THD: +0.04 mg/dL), no difference in quality-adjusted life-years (QALY), and the highest societal costs. DD had a cost-effectiveness ratio of $7,853.6 per 1 mg decrease in phosphorus, compared with EP; and was dominated by THD. Regarding QALY, DD was dominated by EP and THD. The results were sensitive to changes in key parameters. LIMITATIONS: The analysis depended on numerous assumptions. Interpreting the results is limited by the significant baseline differences in key parameters, suggestive of higher baseline societal costs in DD. CONCLUSIONS: DD yielded the greatest effectiveness and decrease in societal costs, but did not affect QALY. Regarding serum phosphorus, DD was likely to be cost-effective compared with EP, but had a low cost-effectiveness probability compared with THD. Regarding QALY, DD was not likely to be cost-effective. Assessing the long-term cost-effectiveness of DD, on similar groups, is recommended.

Serum phosphorus adds to value of serum parathyroid hormone for assessment of bone turnover in renal osteodystrophy.

It is well-established that parathyroid hormone (PTH) correlates with the level of bone turnover in patients with chronic kidney disease stage 5D (CKD-5D). Hyperphosphatemia is a well-established complication of end-stage renal disease and is usually attributed to dietary intake. This study evaluates the relationship between serum phosphorus levels and bone turnover in patients with CKD-5D. 93 patients with CKD-5D from the Kentucky Bone Registry who had sequentially undergone anterior iliac bone biopsies were reviewed. Undecalcified bone sections were qualitatively assessed for turnover and placed into a group with low turnover and a group with non-low (normal/high) turnover. Results of PTH and phosphorus concentrations in blood drawn at the time of biopsies were compared between the groups. PTH and phosphorus levels were significantly higher in the non-low turnover group compared to the low turnover group. Cutoff levels for PTH and phosphorus were tested for predictive power of bone turnover. Both PTH and phosphorus correlated with turnover. Adding serum phosphorus to serum PTH enhanced predictive power of PTH for low turnover. The vast majority of patients with serum phosphorus levels ≥ 6.0 mg/dL had non-low turnover, while the majority of those with low turnover had phosphorus values < 6.0 mg/dL. Classification and regression-tree analysis showed that elevated serum phosphorus (> 6.2 mg/dL) in patients with PTH < 440 pg/mL was helpful in diagnosing nonlow turnover in this range of PTH. In patients with PTH ranges of 440 - 814 pg/mL, serum phosphorus levels > 4.55 mg/dL ruled out low turnover bone disease. This suggests that not only dietary intake but also bone affects serum phosphorus levels.

Micro-CT in the Assessment of Pediatric Renal Osteodystrophy by Bone Histomorphometry.

BACKGROUND AND OBJECTIVES: Computed tomography (CT) measurements can distinguish between cortical and trabecular bone density in vivo. High-resolution CTs assess both bone volume and density in the same compartment, thus potentially yielding information regarding bone mineralization as well. The relationship between bone histomorphometric parameters of skeletal mineralization and bone density from microcomputed tomography (µCT) measurements of bone cores from patients on dialysis has not been assessed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Bone cores from 68 patients with ESRD (age =13.9±0.5 years old; 50% men) and 14 controls (age =15.3±3.8 years old; 50% men) obtained as part of research protocols between 1983 and 2006 were analyzed by bone histomorphometry and µCT. RESULTS: Bone histomorphometric diagnoses in the patients were normal to high bone turnover in 76%, adynamic bone in 13%, and osteomalacia in 11%. Bone formation rate did not correlate with any µCT determinations. Bone volume measurements were highly correlated between bone histomorphometry and µCT (bone volume/tissue volume between the two techniques: r=0.70; P<0.001, trabecular thickness and trabecular separation: r=0.71; P<0.001, and r=0.56; P<0.001, respectively). Osteoid accumulation as determined by bone histomorphometry correlated inversely with bone mineral density as assessed by µCT (osteoid thickness: r=-0.32; P=0.01 and osteoid volume: r=-0.28; P=0.05). By multivariable analysis, the combination of bone mineral density and bone volume (as assessed by µCT) along with parathyroid hormone and calcium levels accounted for 38% of the variability in osteoid volume (by histomorphometry). CONCLUSIONS: Measures of bone volume can be accurately assessed with µCT. Bone mineral density is lower in patients with excessive osteoid accumulation and higher in patients with adynamic, well mineralized bone. Thus, bone mineralization may be accurately assessed by µCT of bone biopsy cores. Additional studies are warranted to define the value of high-resolution CT in the prediction of bone mineralization in vivo.

Informe técnico sobre cobertura en pacientes con diagnóstico de raquitismo renal hipofosfatémico / Technical report on coverage in patients with hypophosphatemic renal rickets

Al respecto de los productos farmacéuticos solicitados se evidencia que en el Petitorio Nacional Único de Medicamentos - PNUME vigente sólo se ha incluido al Calcitriol de 1mcg/mL y el Calcitriol de 0.25 mcg, no encontrándose Solución de Joulie (fosfato disódico+ácido fosfárico), Litiasin (citrato de potasio+ácido cítrico), Solución de Sholl (solución de citratos), K-phos neutral (fosfato de sodio y potasio) y Phospha neutral (anhidrido fosfato de sodio dibásico+fosfato de potasio monobásico+monohidrato fosfato de sodio monobásico), por lo que estos productos deberán contar con la aprobación del Comité Farmacoterapéutico correspondiente para que de corresponder la IPRESS que brinda atención al paciente solicite, de acuerdo a normativa vigente, su evaluación para cobertura SIS.(AU)