Bone Quality in Chronic Kidney Disease Patients: Current Concepts and Future Directions – Part II

Background: Patients with chronic kidney disease (CKD) have an increased risk of osteoporotic fractures, which is due not only to low bone volume and mass but also poor microarchitecture and tissue quality. The pharmacological and nonpharmacological interventions detailed, herein, are potential approaches to improve bone health in CKD patients. Various medications build up bone mass but also affect bone tissue quality. Antiresorptive therapies strikingly reduce bone turnover; however, they can impair bone mineralization and negatively affect the ability to repair bone microdamage and cause an increase in bone brittleness. On the other hand, some osteoporosis therapies may cause a redistribution of bone structure that may improve bone strength without noticeable effect on BMD. This may explain why some drugs can affect fracture risk disproportionately to changes in BMD. Summary: An accurate detection of the underlying bone abnormalities in CKD patients, including bone quantity and quality abnormalities, helps in institution of appropriate management strategies. Here in this part II, we are focusing on advancements in bone therapeutics that are anticipated to improve bone health and decrease mortality in CKD patients. Key Messages: Therapeutic interventions to improve bone health can potentially advance life span. Emphasis should be given to the impact of various therapeutic interventions on bone quality

Bone Quality in CKD Patients: Current Concepts and Future Directions – Part I

Background: There is ample evidence that patients with CKD have an increased risk of osteoporotic fractures. Bone fragility is not only influenced by low bone volume and mass but also by poor microarchitecture and tissue quality. More emphasis has been given to the quantitative rather than qualitative assessment of bone health, both in general population and CKD patients. Although bone mineral density (BMD) is a very useful clinical tool in assessing bone strength, it may underestimate the fracture risk in CKD patients. Serum and urinary bone biomarkers have been found to be reflective of bone activities and predictive of fractures independently of BMD in CKD patients. Bone quality and fracture risk in CKD patients can be better assessed by utilizing new technologies such as trabecular bone score and high-resolution imaging studies. Additionally, invasive assessments such as bone histology and micro-indentation are useful counterparts in the evaluation of bone quality. Summary: A precise diagnosis of the underlying skeletal abnormalities in CKD patients is crucial to prevent further bone loss and fractures. We must consider bone quantity and quality abnormalities for management of CKD patients. Here in this part I, we are focusing on advances in bone quality diagnostics that are expected to help in proper understanding of the bone health in CKD patients. Key Messages: Assessment of bone quality and quantity in CKD patients is essential. Both noninvasive and invasive techniques for the assessment of bone quality are available

Outcome of Patients With Small Vessel Vasculitis After Renal Transplantation: National Database Analysis

Background. Small vessel vasculitis commonly affects the kidney and can progress to end-stage renal disease. The goal of this study is to compare outcomes of patients who received a renal transplant as a result of small vessel vasculitis (group A) with those who received kidney transplants because of other causes (group B). Methods. This is a retrospective analysis of United Network for Organ Sharing registry data for adult primary kidney transplants from January 2000 to December 2014. Group A patients (N = 2196) were compared with a group B (N = 6588); groups were case matched for age, race, sex, donor type, and year of transplant in a 1:3 ratio. Results. Renal and patient survivals were better in the group A (P \u3c 0.001). New-onset diabetes after transplant developed in 8.3% of the group A and 11.3% of group B (P \u3c 0.001). Seventeen (0.8%) patients in group A developed recurrent disease. Of these, 7 patients had graft failure, 3 of which were due to disease recurrence. Group A patients had significantly higher risk of developing posttransplant solid organ malignancies (11.3% vs 9.3%, P = 0.006) and lymphoproliferative disorder (1.3% vs 0.8%, P = 0.026). Independent predictors of graft failure and patient mortality were recipients\u27 morbid obesity, diabetes, age, and dialysis duration (hazard ratio of 1.7, 1.4, 1.1/10 years, and 1.1/year for graft failure, and 1.7, 1.7, 1.6/10 years and 1.1/year for patient mortality, respectively). Conclusions. Renal transplantation in patients with has favorable long-term graft and patient outcomes with a low disease recurrence rate. However, they may have a higher risk of developing posttransplant malignancies

Effect of chronic hepatitis C virus infection on bone mineral density in pediatric renal transplant recipients

Previous studies have suggested that loss of bone mineral density (BMD) frequently occurs in patients with chronic viral liver disease, presenting with histologically proven liver cirrhosis. However, little is known about the occurrence of bone disease in non-cirrhotic patients with chronic hepatitis C virus (HCV) infection. Furthermore, to the best of our knowledge, such an effect has never been studied in pediatric renal transplant recipients. The aim of this study was to assess the impact of HCV infection on BMD in pediatric renal transplant patients. We performed a cross-sectional study to assess BMD and HCV in 83 patients who received living renal allotransplants in the Mansoura Urology and Nephrology Center between 1983 and 2005. The mean age of the study patients at transplantation was 13.4 ± 2.9 years; there were 53 males (63.9%) and 30 females (36.1%). BMD was studied using dual energy X-ray absorptiometry at various time intervals up to 16 years after transplantation (mean duration after transplantation was 48 ± 34 months, range 12- 192 months). Thirty-three patients tested positive for HCV-RNA (positive group) and 50 patients were negative (negative group), and we compared the BMD between the two groups. Before transplantation, 58 patients (69.9%) were on maintenance hemodialysis, four (4.8%) were on peritoneal dialysis and 21 (25.3%) were pre-emptive. Among the HCV-positive group, six patients (18.2%) had osteoporosis, 17 (51.5%) had osteopenia and ten (30.3%) had normal BMD. In the HCV-negative group, ten patients (20.0%) had osteoporosis, 24 (48.0%) had osteopenia and 16 (32.0%) had normal BMD. The difference was not significant between the two groups (P = 0.9). Also, there was no significant difference in the serum creatinine, calcium, phosphorus and parathormone levels between the two groups. Our results suggest that chronic HCV infection does not pose a risk for low BMD in pediatric renal transplant recipients

Effect Of Hepatitis C Virus Infection On Haematocrit And Haemoglobin Levels In Egyptian Hemodialysis Patients

Aim: Hepatitis C virus (HCV) infection is common among the Egyptians. This prevalence is higher among hemodialysis (HD) patients in whom anemia is a common finding. Recently, some case reports and few studies indicated that red cell status increased after hepatitis C viral infection among HD patients. The aim of our study is to investigate whether HCV-positive HD patients have higher hemoglobin (Hb) and hematocrit (HCT) values compared to HCV-negative patients. Methods: Ninety-nine chronic (HD) patients were the subject of this study. Their HCV status was determined by anti-HCV antibodies and confirmed with RNA polymerase chain reaction (PCR). Those with a history of blood transfusion or massive blood loss during the last 6 months were excluded from the study. Results: 70.7% of our patients tested positive for anti-HCV antibody (56.9 % were male). The mean age for HCV positive group was (40.41±14.17 years) while it was (47.35±19.18 years) for HCV negative group (P=0.08). HCV positive group has a longer hemodialysis duration (66.54 ± 43.92 months) compared to HCV negative patients (30.96±23.17 months, P=0.006). Mean Hb was similar in HCV-positive compared to HCV negative group (10.32±2.03 versus 10.22±1.52 gm/dl respectively) (P=0.63). Mean HCT values were also similar in both groups being 30.94± 6.089% in HCV positive versus 30.77± 4.53% in HCV negative group, respectively (P= 0.094). Fifty-five patients (39 HCV positive and 16 were HCV negative) received erythropoietin (EPO) therapy whilst only twenty patients received IV iron. Mean Erythropoietin dose was 5000±2236.06 Units/week in HCV- positive patients versus 6250±2720.29 Units /week in HCV - negative group (P=0.09). Liver function tests were normal except for alanine aminotransferase (ALT) that was significantly higher among HCV-positive compared to HCV-negative patients (31.75±36.4 vs 15.1±7.21 U/L, P=0.05). Conclusion: HCV-positive and HCV-negative Egyptian chronic hemodialysis patients have comparable hemoglobin as well as hematocrit levels and the erythropoietin dose was not influential as its lower value in HCV-positive patients did not reach a statistically significant level

Secondary Osteoporosis and Metabolic Bone Diseases

Fragility fracture is a worldwide problem and a main cause of disability and impaired quality of life. It is primarily caused by osteoporosis, characterized by impaired bone quantity and or quality. Proper diagnosis of osteoporosis is essential for prevention of fragility fractures. Osteoporosis can be primary in postmenopausal women because of estrogen deficiency. Secondary forms of osteoporosis are not uncommon in both men and women. Most systemic illnesses and organ dysfunction can lead to osteoporosis. The kidney plays a crucial role in maintaining physiological bone homeostasis by controlling minerals, electrolytes, acid-base, vitamin D and parathyroid function. Chronic kidney disease with its uremic milieu disturbs this balance, leading to renal osteodystrophy. Diabetes mellitus represents the most common secondary cause of osteoporosis. Thyroid and parathyroid disorders can dysregulate the osteoblast/osteoclast functions. Gastrointestinal disorders, malnutrition and malabsorption can result in mineral and vitamin D deficiencies and bone loss. Patients with chronic liver disease have a higher risk of fracture due to hepatic osteodystrophy. Proinflammatory cytokines in infectious, autoimmune, and hematological disorders can stimulate osteoclastogenesis, leading to osteoporosis. Moreover, drug-induced osteoporosis is not uncommon. In this review, we focus on causes, pathogenesis, and management of secondary osteoporosis

Outcome of Patients With Small Vessel Vasculitis After Renal Transplantation: National Database Analysis

Background. Small vessel vasculitis commonly affects the kidney and can progress to end-stage renal disease. The goal of this study is to compare outcomes of patients who received a renal transplant as a result of small vessel vasculitis (group A) with those who received kidney transplants because of other causes (group B). Methods. This is a retrospective analysis of United Network for Organ Sharing registry data for adult primary kidney transplants from January 2000 to December 2014. Group A patients (N = 2196) were compared with a group B (N = 6588); groups were case matched for age, race, sex, donor type, and year of transplant in a 1:3 ratio. Results. Renal and patient survivals were better in the group A (P < 0.001). New-onset diabetes after transplant developed in 8.3% of the group A and 11.3% of group B (P < 0.001). Seventeen (0.8%) patients in group A developed recurrent disease. Of these, 7 patients had graft failure, 3 of which were due to disease recurrence. Group A patients had significantly higher risk of developing posttransplant solid organ malignancies (11.3% vs 9.3%, P = 0.006) and lymphoproliferative disorder (1.3% vs 0.8%, P = 0.026). Independent predictors of graft failure and patient mortality were recipients' morbid obesity, diabetes, age, and dialysis duration (hazard ratio of 1.7, 1.4, 1.1/10 years, and 1.1/year for graft failure, and 1.7, 1.7, 1.6/10 years and 1.1/year for patient mortality, respectively). Conclusions. Renal transplantation in patients with small vessel vasculitis has favorable long-term graft and patient outcomes with a low disease recurrence rate. However, they may have a higher risk of developing posttransplant malignancies

Is Adynamic Bone Always a Disease? Lessons from Patients with Chronic Kidney Disease

Renal osteodystrophy (ROD) is a common complication of end-stage kidney disease that often starts early with loss of kidney function, and it is considered an integral part in management of patients with chronic kidney disease (CKD). Adynamic bone (ADB) is characterized by suppressed bone formation, low cellularity, and thin osteoid seams. There is accumulating evidence supporting increasing prevalence of ADB, particularly in early CKD. Contemporarily, it is not very clear whether it represents a true disease, an adaptive mechanism to prevent bone resorption, or just a transitional stage. Several co-players are incriminated in its pathogenesis, such as age, diabetes mellitus, malnutrition, uremic milieu, and iatrogenic factors. In the present review, we will discuss the up-to-date knowledge of the ADB and focus on its impact on bone health, fracture risk, vascular calcification, and long-term survival. Moreover, we will emphasize the proper preventive and management strategies of ADB that are pivotal issues in managing patients with CKD. It is still unclear whether ADB is always a pathologic condition or whether it can represent an adaptive process to suppress bone resorption and further bone loss. In this article, we tried to discuss this hard topic based on the available limited information in patients with CKD. More studies are needed to be able to clearly address this frequent ROD finding