Renal osteodystrophy is a common complication among dialysis patients. Factors implicated in the pathogenesis of renal osteodystrophy include the inability of diseased kidneys to produce 1,25 dihydroxycholecalciferol, Phosphate retention, hypocalcemia and secondary hyperparathyroidism. Less common causes, usually associated with dialysis, include Aluminium toxicity and accumulation of B-2 microglobulin.
The disease is classified into four main categories; high turnover bone disease (osteitis fibrosa) more common with hemodialysis, low turnover bone disease (adynamic bone disease and osteomalacia) more common with peritoneal dialysis, mixed uremic osteodystrophy (osteitis fibrosa and osteomalacia), and aluminium related bone disease.
In developing countries, renal osteodystrophy is sometimes overlooked and in many cases considered a luxury to treat.
There are also differences in the pathogenetic causes as well as in the management. Such differences are due to dialysis quality, types of membranes, dialysate water purity, lack of technical facilities to perform and interpret bone biopsies and economic factors hampering the use of effective yet more expensive phosphate binders and active vitamin D.
The Egyptian renal data system showed a renal osteodystrophy prevalence of 33.3% among dialysis patients1. In Poland, renal osteodystrophy among uremic children showed a prevalence of adynamic bone disease in 27%, normal bone histology in 37%, osteomalacia in 2%, mixed lesion in 10% and hyperparathyroidism in 24%. There was no difference in prevalence between children on CAPD and HD2.
In Israel, 66.7% were found to have signs of osteodystrophy3. In the Czech Republic, the prevalence of renal osteodystrophy is 57% among uremic patients4. In Thailand, adynamic bone disease was found in 41.1%, hyperparathyroid in 28.6%, mixed type in 19.6%, mild lesion in 5.4%, osteomalacia in 3.6%, and osteosclerosis in 1.8%. Two cases of aluminum related bone disease were found5.
In Iberoamerica, among 1,209 bone biopsies from 5 different countries (Brazil, Uruguay, Argentina, Portugal, and Spain) showed that low turnover osteomalacia and mixed uremic osteodystrophy were more common in Brazil, Uruguay, and Argentina than in Portugal and Spain whereas predominant hyperparathyroid bone disease was seen more often in Portugal and Spain. Aluminum is still implicated in a great percentage of low bone remodeling lesions in Iberoamerica6. In Singapore, skeletal survey was positive for renal bone disease in 24.4% of patients7. In Turkey, among children with CRF undergoing CAPD, high turnover renal osteodystrophy was the most common bone disease (47%), low turnover bone disease in 29%, and 24% had mixed ROD8.
Ethnic factors also contribute. The distribution of renal osteodystrophy in one study was different among Asians from that of Western countries in pre-dialysis patients. Asian patients had more mild form of osteitis fibrosa and normal findings, and less severe form osteitis fibrosa and aplastic bone disease. Aluminum-related bone disease was not observed9.
Hyperphosphatemia is present in about 50% of dialysis patients. Control of hyperphosphatemia poses a major problem worldwide. The problem is even greater in developing countries due to inadequate nutritional assessment, the use of aluminum containing phosphate binders, which though cheaper and effective; increase the hazard of aluminum bone disease, and the inability to afford the high cost of the more effective phosphate binders. One solution for the problem of hyperphosphatemia in developing countries my be the use of extended dialysis time for more hours rather than the standard 4 hours dialysis. This would allow better clearance of phosphate without adding much cost.
Active forms of vitamin D, an essential part in the management of renal osteodystrophy is often an expensive drug that is not readily available to all patients. Newer vitamin D3 analogues are even more expensive. Many dialysis patients rely on calcium preparations to control hypocalcemia. In developing countries, the use of cheaper forms of vitamin D as Dihydrotachysterol for the correction of hypocalcemia may be warranted.
Aluminum related bone disease in dialysis patients is seldom seen in developed countries nowadays due to proper reverse osmosis water treatment. This problem is still a health hazard in countries lacking proper water treatment for dialysis either due to limited financial resources or lack of water quality control. The use of aluminum containing phosphate binders also contributes in aluminum toxicity in dialysis patients. This problem is augmented by the limited facilities to diagnose increased aluminum levels in water. In Brazil, aluminum overload was observed in 74 of 96 patients. These data show a high prevalence of aluminum overload in Brazilian patients10. In Greece, bone aluminum deposition was found in 58% of dialysis patients11.
Iron overload is also incriminated in developing countries.
There is experimental and clinical evidence that iron overload is associated with impaired bone formation. In chronic renal failure, low rates of bone formation (aplastic bone disease) have been associated with iron rather than aluminum overload12. Both iron and aluminum have been identified at the interface between osteoid and mineralized bone, in bone marrow macrophages, hepatocytes, kupffer cells and parathyroid cells13. In developing countries, the excessive use of blood transfusion and parenteral iron to treat anemia rather than using the more expensive Erythropoietin may be a contributing factor for the development of renal bone disease.
Strontium is suspected to affect bones. In Turkey, a significant higher prevalence of rickets was found in children living in a region with high soil strontium content than in children living in low strontium region14. A worldwide multicenter study involving 834 patients from 34 dialysis centers in 23 countries revealed high levels of strontium mainly in developing countries. High strontium levels were found in tap water, decreased after reverse osmosis treatment of water and then increased again by addition of acetate concentrates contaminated with strontium. A direct effect of strontium on bone mineralization is suggested by strontium localization in calcified bone using histochemistry and electron probe microanalysis15.
B-2 microglobulin associated amyloidosis occurs in both hemodialysis and CAPD patients. The influence of hemodialysis on kinetics of circulating B2M has been examined in many studies. The characteristics of the dialysis membranes, namely structure, surface area, permeability and biocompatibility, play an important role in removal of B2M. The use of cuprophane and cellulose acetate membranes does not allow removal of significant amounts of B2M whereas the use of highly permeable membranes such as polysulfone or polyacrylonitrile allows removing more of the offending polypeptide16. The purity of dialysis water has been incriminated also in the pathogenesis of B-2 microglobulin associated amyloidosis. Ultra pure dialysate may be partially protective or at least delay the onset of dialysis amyloidosis17. The use of biocompatible high flux membranes and ultra pure dialysate in developing countries is linked to economic issues and is difficult to implement.
REFERENCES
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