Metabolic bone disease in chronic renal failure. I. Dialyzed uremics.

Garner and ball's point counting technic was used to compare metabolic bone disease in dialyzed and nondialyzed uremic patients. Histologic measurements of bone from dialyzed and nondialyzed uremic patients dying between 1966 and 1971 showed that dialyzed patients have quantitatively more severe bone resorption, distortion of trabecular architecture and mineralization defects. Mineralization defects become more severe as the duration of dialysis increases but are not related to serum calcium and phosphorus levels. Bone volume in both groups is normal or increased and in dialysis patients increases in proportion to the elevation of serum phosphorus. Mean serum phosphorus and calcium levels, bone volume, and volume: surface ratios all decreased in dialysis patients between 1966 and 1971, while bone resorption and mineralization defects did not change. These results suggest that lowering of serum phosphorus without increasing serum calcium may aggrevate the uremic bone disease by reducing bone volume without improvement of mineralization and resorption defects.     

Effect of renal transplantation on marrow mast cell hyperplasia of chronic renal failure.

Marrow mast cells have been counted in iliac bone from patients with chronic renal failure treated by renal transplantation. Mast cell numbers were initially increased but returned to the normal range in many patients after renal transplantation. Improvement in osteitis fibrosa and osteomalacia after transplant was not clearly related to this diminution in the number of mast cells. The use of prednisone in renal transplant patients may have some effect in reducing the numbers of mast cells. There is no fully acceptable explanation for the increase in marrow mast cells which occurs in chronic renal failure.     

Metacarpal bone measurements in renal transplant recipients, in corticosteroid-treated patients with polymyalgia rheumatica and in patients with primary hyperparathyroidism

Quantitative radiological measurements on the second left metacarpal bone were carried out in 23 patients with primary hyperparathyroidism, 22 corticosteroid-treated patients with polymyalgia rheumatica and 40 renal transplant recipients treated with prednisone and azathioprine. Women with primary hyperparathyroidism and corticosteroid-treated women showed significantly decreased mean values of metacarpal bone compared to normal controls, probably due to a higher bone resorption than formation at the endosteal surface. Bone loss was more pronounced in corticosteroid-treated women than in women with primary hyperparathyroidism, partly due to age difference. In renal transplant recipients, bone loss took place during the initial period after renal transplantation, probably due to increased endosteal bone resorption. During this period a periosteal new bone formation took place in female renal transplant recipients. The quantitative radiological measurements make it possible to determine whether bone loss is due to a higher ratio of bone resorption than of bone formation at the periosteal and/or endosteal surface.     

Deranged mineral content in the bone of patients with chronic renal failure, estimated by computed tomography

To evaluate the extent of renal osteodystrophy in patients with chronic renal failure, the CT numbers of the lateral condylus and mid-shaft of the femur were measured. To adjust for variation due to measurement conditions, calibration phantom was simultaneously scanned with the femur. The CT numbers of the lateral condylus were significantly lower than the control in both nondialyzed (p less than 0.005) and dialyzed patients (p less than 0.05). The CT numbers of the mid-shaft of the femur in dialyzed patients correlated significantly to the duration of hemodialysis (r = 0.807, p less than 0.001). In 15 patients subjected to both CT scan and the photon absorptiometry, the CT numbers of the lateral condylus positively correlated to the mineral content of the radial (r = 0.57) and ulnar (r = 0.69) bones as calculated by photon absorptiometry. These results indicate that the CT scan can be used to estimate bone mineral content quantitatively, and is useful tool for evaluating renal osteodystrophy in patients with chronic renal failure.     

Relative importance of renal failure and increased bone resorption in the hypercalcaemia of myelomatosis.

In order to define the relative importance of renal failure and increased bone resorption in the hypercalcaemia of myelomatosis 22 untreated patients were studied, of whom 12 were hypercalcaemic. Most patients had malabsorption of radiocalcium from the gastrointestinal tract and evidence of increased bone resorption as assessed by fasting urinary hydroxyproline/creatinine ratio. The mean OHPr/Cr ratio, however, was similar in patients with and without hypercalcaemia. Renal failure and Bence Jones proteinuria occurred more frequently in the hypercalcaemic patients. In four patients with hypercalcaemia there was an increase in OHPr/Cr after saline infusion accompanied by an improvement in renal function and hypercalcaemia. Mithramycin given to the same patients further reduced hypercalcaemia, presumably by inhibiting bone resorption. It was concluded that the hypercalcaemia of myelomatosis is due to the combination of renal failure and increased bone resorption, but that the OHPr/Cr ratio in the untreated state is a poor indicator of the degree of bone resorption in hypercalcaemic patients.     

Deranged Ca, Al and Mg content in the tissues of patients with chronic renal failure, as measured by non-destructive neutron activation analysis

Ca, Al and Mg content in the bone, aorta, skin and hair of 55 persons was measured by non-destructive neutron activation analysis. The Ca content in the bone of nondialyzed and dialyzed patients was found to decrease. Al and Mg were relatively higher than Ca in the patients compared to the controls. The present study suggests that fluctuation in the content of Al and Mg may have some relation to renal osteodystrophy such as osteomalacia as well as similar and related disorders. Al and Mg content in the aorta, and that of Ca in the hair of uremic patients, were higher than the controls. The mean Ca content in the skin of the patients was 25% higher than the controls. These findings indicate 1) that Al and Mg are possibly related to the advance of osteodystrophy, and 2) that Ca, Al and Mg deposits in the organs of uremic patients are a reflection of metabolic disorders in chronic renal failure.     

Renal osteodystrophy in predialysis patients without stainable bone aluminum. A cross-sectional bone-histomorphometric study

Histomorphometry was performed on transiliac bone biopsies, double-labeled with tetracycline, from 60 consecutively admitted patients (20 women) at various stages of chronic renal failure (CRF). Eleven patients (1 woman) had normal bone resorption and formation indices. Bone resorption and osteoid formation increased with progression of renal failure, but abnormal values were seen even at slightly elevated creatinine levels. Mineralization lag time increased with CRF duration; prolonged values were only seen in patients with polycystic kidney disease or chronic pyelonephritis with advanced CRF. All patients with impaired mineralization also had increased bone resorption. Diabetes mellitus did not protect against skeletal lesions. The biochemical tests were too insensitive to predict type or severity of bone disease, and hand X-rays had no diagnostic value in early stages of renal osteodystrophy.     

Pulmonary pathology in renal transplant recipients

Studies of the lungs have revealed multiple functional and histopathological abnormalities in patients with chronic renal failure, but data following renal transplantation are extremely limited. We examined postmortem data from 20 transplant patients and found pulmonary abnormalities in most patients. The number of pulmonary abnormalities noted in patients with poor transplantation, averaged 5.3 per patient. The corresponding number was significantly less (3.4 per patient) in the group with good transplant renal function, surviving more than one year after transplantation. Pulmonary calcification, fibrosis, and hemosiderosis were found in several patients in the former group but in none of the latter group. This observation suggests reversibility of these pulmonary abnormalities with successful renal transplantation.     

Immunosuppressive therapy and bone metabolism after kidney transplantation

The success of transplant medicine due to improvements of immunosuppressive therapy has led to a significant increase of patient and organ survival. With the increasing number of transplantations, however, long term complications, often affecting the skeletal system, are becoming more frequent. Bone alterations often exist prior to transplantation in patients with chronic renal failure. There are two types of renal osteopathy, including "low-turnover bone disease", consisting of osteomalacia, and adynamic bone disease, and "high-turnover bone disease" due to the development of secondary hyperparathyroidism. Many patients show evidence of both disorders (mixed bone disease). During the first months after transplantation patients lose bone mass rapidly. One of the major factors responsible for the development of osteoporosis is thought to be the intensive immunosuppressive therapy during that period, steroids in particular seem to play an important role. To what extent other medications influence bone metabolism has not been established. Currently there are no studies about a standardized therapy and treatment relies mainly on experience with other forms of osteoporosis.     

The peculiarities of bone exchange disorder and its regulation in men after long terms following orthotopic heart transplantation and cadaveric kidney transplantation

The study found bone exchange disorder manifested by accelerated bone resorption, retarded bone formation, and the loss of the bone mineral density (BMD) of the axial and peripheral skeleton in 19 men (39 observations) 66 +/- 44 months following orthotopic heart transplantation (OTHT) and in 92 men 45 +/- 28 months after cadaveric kidney transplantation. An accelerated bone resorption, more pronounced in cadaveric kidney (CK) recipients, is associated with hyperparathyroidism (HPT) and renal dysfunction, while bone formation retardation is associated with a decrease in insulin-like growth factor-1 level. An increase in osteoprotegerin level is of compensatory character. The prominence of HPT depends on the degree of renal dysfunction; in CK recipients it also depends on the degree of the reduction in the levels of biologically active testosterone and estradiol. Reduction in BMD of the peripheral skeleton after OTHT are associated with the degree of renal dysfunction and a decrease in free testosterone index; after CK transplantation it is associated with HPT, the cumulative dose of glucocorticoids, reduction in the levels of biologically active testosterone and estradiol, as well as sex-hormone binding globulin (SHBG); reduction in spine BMD is only associated with SHBG.     

肾移植术后感染性腹泻的诊疗分析

肾移植是挽救晚期慢性肾衰竭患者的最佳方式,与长期透析比较可使患者获得更长久的生存率,但由于术后需要长期服用免疫抑制剂和相对较长时间的抗生素,极易容易引起肠道菌群紊乱和肠道感染,导致腹泻的发生。本文着重回顾了有关肾移植受者感染性腹泻的现有文献,对肾移植后感染性腹泻的研究进展进行了总结,并希望为临床能寻找到高效可靠的移植后感染性腹泻的评估方法提供一定的思路。     

Is secondary hyperparathyroidism-related myelofibrosis a negative prognostic factor for kidney transplant outcome?

Secondary hyperparathyroidism (HP) presenting with hypocalcemia and subsequent increased parathormone (PTH), is mainly identified in patients with chronic renal failure, which has been associated with variable degrees of bone marrow fibrosis.For suitable patients with end-stage renal disease (ESRD), kidney transplantation is recognized as the therapy of choice, being superior to dialysis in terms of quality of life and long-term mortality risk; in this regard interesting data show that increased time on dialysis prior to kidney transplantation is associated with decreased graft and patient survival.In our opinion an important and until now underestimated determinant of graft survival is the proper activity of bone marrow because of the emerging role of hematopoietic stem cells (HSC) in repair of ischemia/reperfusion (IR) damage. We postulate that in ESRD patients, who usually undergo long dialytic treatment, a myelofibrosis caused by an overt secondary HP could drastically decrease the HSC potential for IR damage repair after kidney transplant; this could irremediably lead to a delay in graft function with all related complicances.If the curative role of bone marrow-derived stem cells was confirmed by more data obtained in experimental animal models, it could be possible to try a cellular-based therapeutic approach in the management of ESRD patients which are in waiting list for a kidney transplant.     

Prevention of postoperative acute renal failure

Postoperative acute renal failure (PO-ARF) is a serious complication resulting in a prolonged stay and high mortality. Patients may be at risk for this problem because of an underlying medical illness, nature of surgery, nephrotoxin exposure, or combinations of these factors. An increase in the intra abdominal pressure above 20-mm Hg is associated with an increase in the incidence of PO-ARF. Based on many clinical studies in high-risk surgical patients and patients undergoing renal transplantation, the only proven management strategies for prevention of PO-ARF are adequate volume expansion and avoidance of hypovolaemia. Drugs known to be nephrotoxic should be avoided or used with caution. Three main pharmacological agents namely mannitol, frusemide and dopamine have been extensively tried in the prevention of PO-ARF. Mannitol has proven of value only in the presence of adequate volume expansion in attenuating renal dysfunction in transplant patients. Frusemide converts oliguric renal failure to non-oliguric renal failure. The bulk of the data, including that from prospective studies indicate dopamine is only a diuretic. Fenoldopam, a dopamine analogue, has shown early promise in reports. Calcium channel blockers have not been shown to improve the outcome in renal transplantation or help in the prevention of contrast-induced nephropathy. Atrial natriuretic peptide has not been proven to be of benefit in established renal failure and its role in prevention has not been assessed.     

Importance of biochemical indicators of bone turnover in patients on chronic dialysis and after kidney transplantation

Bone remodeling is a continuous process of removal of microscopic amounts of bone tissue due to synchronized actions of osteoclasts and osteoblasts with the purpose of renewal and repair of bone tissue. During the formation of bone matrix osteoblasts synthesize proteins. Measurement some of these proteins in blood has clinical significance as indicators of bone formation: osteocalcin, procollagen type I propeptide, and bone alkaline phosphatase. During osteoclastic bone resorption, collagen type I breakdown fragments are released in the circulation and excreted in the urine, and measured in serum or urine as bone resorption markers (telopeptide, pyridynolines). Bone metabolism and accordingly bone markers are subjected to considerable biologic variation. The effects of age, sex, race, pregnancy and lactation, fracture, disease and certain drugs cannot be avoided and must thus be considered when interpreting the results. Circadian variation is excluded by obtaining samples in the morning and the effect of exercise prevented. The use of bone markers has been extensively studied in monitoring the effect of antiresorptive treatment in osteoporotic women. A decrease of 30-50% occurs within 3 months after the beginning of hormone replacement therapy or bisphosphonates and remains at this level. In patients on chronic dialysis treatment, bone markers are increased and reflect bone metabolism as assessed by bone biopsy. Although bone markers enable discrimination between high and low bone turnover, they cannot substitute for bone biopsy in determination of the type of renal osteodystrophy. The factors affecting bone disorder in these patients, i.e. dialysis duration or parathyroid function correlate with bone markers. In kidney transplant recipients, an increased bone turnover and its normalization after approximately 2 years can be assessed by bone markers. Similar to chronic dialysis, risk factors for bone disorder after kidney transplantation (e.g., dialysis duration, parathyroid function, age, sex, immunosuppressants, corticosteroids, graft function) are associated with bone markers. We present cross-sectional and longitudinal data on 100 patients on chronic dialysis and 80 kidney transplant recipients. In conclusion, sufficient evidence exists indicating that the measurement of bone markers enables assessment of bone turnover and its dynamics. However, no guidelines or recommendations have been put forward to validate their use in routine clinical practice of chronic dialysis or kidney transplantation bone disorders.     

Recovery of organ dysfunction during bridging to heart transplantation in children and adolescents

The beneficial effects of ventricular assist devices on organ dysfunction during bridging to heart transplantation have been widely reported in the adult population. In contrast, the use of ventricular assist devices used as bridge-to-transplant in children is limited. To evaluate organ recovery during ventricular support in pediatric transplant candidate, respiratory, renal and hepatic function were reviewed retrospectively. The Thoratec device (stroke volume 65 ml) and the HIA-Medos-system (stroke volume 25/10 ml) were used as bridge-to transplant in 11 children and adolescents who were in low-output-syndrome despite maximal pharmacological support. Prior to implantation five patients were mechanically ventilated, six patients underwent cardiopulmonary resuscitation, eight patients had anuria (one treated by hemofiltration), three patients had liver dysfunction and four patients had signs of severe infection. At the time of implantation one patient was supported by the intraaortic balloon pump and one by the femorofemoral bypass for rapid hemodynamic stabilization. Eight patients were treated using the Thoratec device (one of these by Nova cor on the left side), three by the HIA-Medos system. The support time ranged between seven and 140 days. Seven patients could be extubated within three days. Renal function recovered in all pts. Liver enzymes decreased in all pts without reaching normal values. Bilirubin values also decreased in survivors but increased to 9.3 mg/dL in non-survivors. At least seven patients underwent successful heart transplantation, three patients died because of multiorgan failure after extended transfusion and one patient because of technical failure. In our experience the hemodynamic situation was sufficient in all bridging to transplant candidates. In all patients who underwent successful transplantation, transplantability was associated with rapid organ recovery within seven days after initiating mechanical assistance. Extended blood tranfusions, combined failure of three organs and increasing bilirubin values during support seem to be predictors of poor outcome.     

Effects of 1-alpha OH D3 therapy in uremic patients in conservative or dialytic treatment.

The effects of phosphate restriction and of 1 alpha OH D3 administration were investigated in patients with advanced chronic renal failure. Few modifications of the various biochemical parameters in the patients were achieved with the restriction of dietary phosphate while better results were obtained with 1 alpha OH D3 administration. In dialyzed patients the treatment with this drug resulted in a normalization in serum calcium and alkaline phosphatase levels and in a remarkable significant decline in plasma parathyroid hormone and a reduction in the bone disease associated with uremia. This treatment in dialyzed uremic patients could avoid the employment of higher dialysate calcium concentration potentially dangerous for postdialysis hypercalcemia with the risk of metastatic calcifications.     

Hyperparathyroidism and bone disease after renal transplantation

Metabolic bone disease is one of the most frequent complications of chronic renal failure. Numerous disorders leading to the metabolic bone disease can be reversed by successful renal transplantation. However, in some patients, in spite of satisfactory renal function, some disorders may persist for months after successful transplantation, e.g. increased parathyroid hormone secretion. Besides, drugs used in immunossuppressive therapy may cause metabolic bone disease or reduction of of bone mass. Therefore, significant loss of mass takes place in the majority of patients during the first six months. Among drugs used in the prevention of bone disease after transplantation of solid organs the most important role have biphosphonates and vitamin D, i.e. calcitriol.     

Acid phosphatase, beta-glucuronidase and N-acetyl-beta-D-glucosaminidase activity of peritoneal neutrophils in patients with terminal renal failure treated by intermittent peritoneal dialysis

Acid phoshatase (AcP), beta-glucuronidase (GR) and N-acetyl-beta-D-glucosaminidase (NAG) activity in neutrophils obtained from the peritoneal fluid of 50 patients with terminal renal failure treated by intermittent peritoneal dialysis, and of 30 control subjects with normal renal function was semiquantitatively scored using a cytochemical method. This study was repeated in 22 dialyzed patients during the course of bacterial peritonitis. A significant decrease in the AcP score and an increase in the GR score were found in the neutrophils from dialyzed patients. In dialyzed patients with peritonitis, the GR and NAG scores were higher that in those without this complication.     

Long-term survival and late deaths after allogeneic bone marrow transplantation. Late Effects Working Committee of the International Bone Marrow Transplant Registry.

BACKGROUND AND METHODS: It is uncertain whether mortality rates among patients who have undergone bone marrow transplantation return to the level of the mortality rates of the general population. We analyzed the characteristics of 6691 patients listed in the International Bone Marrow Transplant Registry. All the patients were free of their original disease two years after allogeneic bone marrow transplantation. Mortality rates in this cohort were compared with those of an age-, sex-, and nationality-matched general population. Cox proportional-hazards regression was used to identify risk factors for death more than two years after transplantation (late death). RESULTS: Among patients who were free of disease two years after transplantation, the probability of living for five more years was 89 percent (95 percent confidence interval, 88 to 90 percent). Among patients who underwent transplantation for aplastic anemia, the risk of death by the sixth year after transplantation did not differ significantly from that of a normal population. Mortality remained significantly higher than normal throughout the study among patients who underwent transplantation for acute lymphoblastic leukemia or chronic myelogenous leukemia and through the ninth year among those who underwent transplantation for acute myelogenous leukemia. Recurrent leukemia was the chief cause of death among patients who received a transplant for leukemia, whereas chronic graft-versus-host disease was the chief cause among those who received a transplant for aplastic anemia. Advanced, long-standing disease before transplantation and active chronic graft-versus-host disease were important risk factors for late death. CONCLUSIONS: In patients who receive an allogeneic bone marrow transplant as treatment for acute myelogenous or lymphoblastic leukemia, chronic myelogenous leukemia, or aplastic anemia and who are free of their original disease two years later, the disease is probably cured. However, for many years after transplantation, the mortality among these patients is higher than that in a normal population.