Renal osteodystrophy is a change in bone morphology in patients with chronic kidney disease caused by a violation of bone mineral metabolism. Symptoms include pathological fractures, bone pain, skeletal deformity. Diagnosis is based on biopsy data, radiography, densitometry, CT and MRI, markers of bone metabolism. Treatment involves correction of calcium-phosphorus metabolism: vitamin D metabolites, phosphate-binding agents are prescribed. In the absence of an effect, it is possible to perform a parathyroidectomy, in exceptional cases, kidney transplantation is performed.
ICD 10
N25.0 Renal osteodystrophy
Meaning
The term renal osteodystrophy has been used since 1943, when a link between bone changes and CRF was revealed. In 2006, the name MBD-CKD (mineral and bone disorders associated with chronic kidney disease) was proposed, the pathology began to be considered as a progressive complication of renal failure. The disorder is present in most patients with CKD with a decrease in glomerular filtration rate below 50%, in 90-100% of patients (adults and children) with end-stage CRF who are on replacement therapy. The risk of fractures increases 4-5 times compared to the general population. In patients over 60 years of age, metabolic osteopathy is registered 3 times more often.
Causes
Normally, the bone tissue is constantly being remodeled, and the kidneys maintain normal levels of phosphorus and calcium in the blood. With hypocalcemia of any genesis, the parathyroid glands secrete a hormone that provokes the leaching of the mineral from the bones, which leads to their demineralization. Renal osteodystrophy is one of the signs of chronic renal failure, which is the outcome of many urological and nephrological pathologies. Therefore, diseases that cause CRF are simultaneously considered triggers of bone metabolism disorders:
- Congenital and hereditary diseases. Polycystic kidney disease, Alport syndrome and congenital hypoplasia are often complicated by renal failure with the development of metabolic osteopathy. A burdened family history is typical for these pathologies. The frequency of occurrence is 0.5-3%. In most cases, clinical manifestations of osteodystrophy have been present since childhood (renal rickets).
- Glomerular pathologies. They include primary glomerulonephritis, secondary glomerular kidney disease, characteristic of systemic lupus erythematosus, diabetic nephropathy and hemorrhagic vasculitis. Diabetes mellitus is one of the most frequent causes of the loss of the functional ability of the kidneys, it accounts for 44%, glomerular pathology – 8% of cases.
- Vascular diseases. Atherosclerosis and systemic sclerosis with kidney damage disrupt blood supply, cause tissue ischemia, resulting in progressive death of nephrons. Hypertension, complicated by nephropathy, in 30% of cases leads to CRF and metabolic bone disease. Osteodystrophy is combined with serious complications from the cardiovascular system, associated with high mortality.
- Tubulointerstitial diseases. Tubulointerstitial nephritis, which progresses to CRF with impaired bone metabolism, may be idiopathic, medicinal or immunological in nature. Genitourinary tuberculosis, schistosomiasis, nephrocalcinosis are also manifested by the gradual loss of functional structures of the kidney. The use of antiviral drugs for the treatment of hepatitis B, HIV infection is associated with tubular dysfunction and hypophosphatemic osteomalacia.
- Conditions accompanied by obstruction. Urolithiasis, prostatic hyperplasia, pelvic tumors and retroperitoneal fibrosis are characterized by a violation of adequate urodynamics. Stagnation of urine promotes the reproduction of bacterial microflora, the development of recurrent secondary pyelonephritis with hydronephrotic transformation of the cup-pelvic system. With a bilateral lesion, CKD is attached, triggering the processes of osteodystrophy.
The aggravating factors include improper nutrition, leading to vitamin D hypovitaminosis, a postmenopausal condition accompanied by a violation of mineral metabolism, bad habits. Elderly age, inadequate intake of calcitriol predisposes to renal osteopathy. In patients taking antacids for gastrointestinal ulcers or receiving renal replacement therapy, aluminum accumulates in the body. This is an additional cause of osteomalacia against the background of inhibition of osteoblast activity.
Pathogenesis
Renal osteodystrophy is described as a result of hyperparathyroidism, secondary hyperphosphatemia with hypocalcemia, provoked by a decrease in phosphate excretion by damaged kidneys. The most important reason for the decrease in calcitriol levels in CRF is the high level of fibroblast growth factor 23 (FGF23, phosphatonin), which is produced by osteocytes and osteoclasts in response to hyperphosphatemia. The compound helps to reduce phosphorus reabsorption in the proximal tubules of the nephron, blocks the activity of 1-alpha-hydroxylase.
1-alpha-hydroxylase affects the transformation of 25(OH)D at 1.25(OH)2D and decrease in absorption of vitamin D by the intestinal walls. This compensatory mechanism maintains the level of phosphates in the norm with their increased excretion in the urine. Since a large amount of FGF23 is necessary to maintain normal serum phosphorus levels, calcitriol synthesis is suppressed, which provokes a decrease in Ca absorption, hypocalcemia. This is also facilitated by the destruction of the proximal tubules (the site of calcitriol formation), acidosis on the background of uremia, a decrease in the supply of substances for the production of active hormone.
Hypocalcemia is supported by another compensatory mechanism – increased secretion of parathyroid hormone. Its excessive production increases the rate of resorption, leads to changes in the structure of the skeleton due to secondary hyperparathyroidism. The progression of renal dysfunction with hyperphosphatemia stimulates hyperplasia of the parathyroid glands, hypersecretion of parathyroid hormones, which gradually leads to the development of adenoma. Enhanced bone exchange and remodeling result in a violation of its architectonics, mineralization, and loss of strength.
Classification
The systematization of pathology is based on the evaluation of the results of histological examination of bone biopsies. There are three fundamental processes designated by the English abbreviation TMV: metabolic rate (low, normal, high), bone mineralization (normal, impaired), volume (low, normal, high). The classification was proposed by experts in 2009, based on the correlation between the activity of metabolic processes of bone tissue, morphological changes and the content of intact parathyroid hormone in the blood. Renal osteodystrophy associated with CKD can occur:
- With an increase in metabolic processes. Clinical manifestations include fibrotic osteitis, secondary hyperparathyroidism. Another name is hyperparathyroid bone disease.
- With a decrease in metabolic processes. The group includes adynamic skeletal disease, osteomalacia (demineralization of bone matter, not accompanied by a pronounced change in protein synthesis in the matrix and leading to bone softening).
- In the combined version. The combined form combines moderate secondary hyperparathyroidism (HPT) and osteomalacia.
The most common forms of renal osteopathy include fibrotic osteitis and mixed osteodystrophy (high metabolism), moderate HPT (normal bone metabolism), adynamic bone disease and osteomalacia, which is characterized by a low level of metabolism. Fibrotic osteitis is considered a classic manifestation of HPT and uremia, it occurs in 40%. Osteomalacia and its combined form are found in less than 10% of biopsies. The share of adynamic disease, according to various sources, accounts for from 15-60%.
Symptoms
Pathology includes signs of secondary hyperparathyroidism, rickets, osteomalacia and osteoporosis. Rickets with osteomalacia occur in children, secondary hyperparathyroidism with osteomalacia – in adults. The clinic is variable, it depends on the form of renal osteodystrophy. The disease has been asymptomatic for a long time. Subsequently, patients complain of joint pain, which increases with movement, bone ache. With the accumulation of calcium in the cartilage, there is a limitation of the volume of movements due to the loss of elasticity of the articular surfaces, a duck (waddling) gait appears.
Calcification of the wall of superficial vessels causes calcifylaxis, which is manifested by foci of necrosis on the skin. The process is accompanied by skin itching, which can be temporary or permanent. Calcium is responsible for neuromuscular transmission, its violation is manifested by muscle weakness, which gradually progresses, spreading to the upper extremities. On the part of the nervous system, apathy, constant drowsiness, memory impairment are detected. Cardiovascular manifestations are represented by chest pain, shortness of breath, tachycardia.
Complications
Complications include fractures and deformities of bones, tendon ruptures. From the side of the heart, focal changes of the myocardium are recorded, the clinic resembles a heart attack. Acute hypercalcemic crisis is an urgent condition that requires immediate hospitalization and develops when the Ca level reaches above 3.5 nmol/L. He is characterized by sharp weakness, change of consciousness, abdominal pain, accompanied by indomitable vomiting. The ECG records rhythm disturbances, blockages.
Vascular calcifications leading to atherosclerosis, hypertension, congestive heart failure are considered as complications. The deposition of calcinates in the lungs can cause respiratory failure. Renal osteodystrophy with low metabolism is often accompanied by severe anemia resistant to erythropoietin treatment. At the same time, the general well-being suffers, the quality of life deteriorates significantly. Children develop dwarfism, O-shaped and X-shaped deformities of the lower extremities due to impaired mineral metabolism.
Diagnostics
The diagnosis is established on the basis of complaints, physical examination data, evaluation of the results of laboratory and instrumental studies. Bone biopsy is the most informative, but the intervention is not recommended for all patients because of the invasiveness. The procedure is carried out in specialized clinics to exclude the adynamic form of pathology, in controversial situations or when deciding on the feasibility of surgery. Instrumental and laboratory methods of diagnosing osteodystrophy against the background of kidney disease include:
- Radiography. The primary imaging method used to assess the condition of bone tissue in patients suffering from nephrological and urological diseases. Radiographs visualize fractures, specific skeletal changes in osteodystrophy. Due to radiation exposure, the technique has limitations on the number of studies, especially in childhood.
- Densitometry. Usually, two-energy X-ray absorptiometry is performed in the lumbar spine, proximal femur and distal forearm. The study shows changes typical of osteopenia and osteoporosis, allows you to predict the risk of fractures. The procedure is repeated in dynamics to assess bone density against the background of ongoing therapy. Indications for densitometry are also CRF, planned hemodialysis or transplantation.
- MRI and CT. They are prescribed if other methods are insufficiently informative. Computed tomography provides high-quality visualization of pathological changes in the skeleton that are not detected when performing conventional radiography. MRI makes it possible to assess the condition of adjacent tissues: tendons, ligaments, cartilage.
- Laboratory tests. Evaluation of bone metabolism allows us to judge the degree of tissue remodeling. The Ca level is usually low, the serum P is higher than normal (depends on the stage of CKD). Alkaline phosphatase is elevated due to osteoblastic activity. The best non-invasive way to diagnose subtypes of renal osteodystrophy is to determine the level of PTH to assess bone metabolism.
Differential diagnosis is carried out with myeloma, osteoporosis of extrarenal etiology, resorptive osteomalacia against the background of vitamin D deficiency. The main criterion is the preservation of renal function, urea and creatinine, as a rule, do not exceed the norm or are slightly reduced. The cause of osteomalacia is sometimes idiopathic hypercalciuria, unrelated to acidosis. Scientists suggest that the increased loss of Ca is due to concomitant pyelonephritis with an abnormal structure of the tubules.
Treatment
Substitution therapy without other methods cannot eliminate violations of phosphorus-calcium metabolism and prevent bone pathology in terminal uremia. Electrolyte balance support includes prescribing medications that help to ensure the level of serum calcium and phosphorus as close to normal as possible, and suppress the activity of the parathyroid glands. Adequate treatment of renal osteodystrophy largely determines the quality of life of patients.
Diet is of great importance, because most minerals come from food. Hyperphosphatemia is prevented by limiting foods containing large amounts of protein (meat, milk, eggs). It is important to maintain the concentration of calcium at the upper limit of the norm, for this purpose dark green vegetables, tofu, citrus fruits are included in the diet, according to indications, calcium supplements are additionally administered. The ratio of Ca and P should be 1:1. The doctor constantly monitors blood electrolytes, hormonal profile, adjust the therapy regimen.
Medical treatment
The choice of a particular drug is made taking into account the form of osteodystrophy, the stage of chronic kidney disease, the severity of secondary hyperparathyroidism. The selection takes into account the side effects of taking medications that are detected in the patient. The main groups of medicines include:
- Phosphorus binders. Calcium carbonate and calcium acetate are prescribed from the initial stages of CRF, prevents the absorption of phosphate in the gastrointestinal tract. Their reception is especially relevant for hemodialysis. In case of inefficiency, the approach to RRT is revised: the surface area of the dialysis membrane, the duration of the procedure, and the number of sessions are increased. Previously used preparations based on aluminum hydroxide have now lost relevance due to the risk of accumulation of the compound and related complications. Their best alternative is sevelamer.
- Funds with vitamin D. Calcitriol and alfacalcidol help to reduce the activity of the parathyroid glands. With RRT, they are used for the prevention and treatment of secondary hyperparathyroidism. Persistent hypocalcemia with normal indicators of phosphorus metabolism is corrected by the appointment of vitamin D, which enhances the absorption of Ca. Against the background of the reception, the pain syndrome decreases, the mineralization of bone tissue increases, especially with fibrocystic ostitis.
- Bisphosphonates. The experience of using medicines of this group is insufficient, there is evidence that the drugs prevented bone demineralization after kidney transplantation. RRT and the intake of vitamin D metabolites for the correction of secondary hyperparathyroidism is sometimes complicated by persistent hypercalcemia. Bisphosphonates in such cases contributed to the normalization of the condition, were well excreted from the body using hemodialysis.
Surgical treatment
Removal of parathyroid gland tissue is indicated if the PTH exceeds 800 pg / ml for 3 months, despite conservative therapy and measures taken: withdrawal of vitamin D, refusal to use a dialysis solution with a high Ca content, diet compliance. Recurrent hypercalcemia, the appearance of ischemic necrosis, debilitating itching of the skin also require surgical treatment. The intervention is justified before kidney transplantation, since the postoperative period is accompanied by hypercalcemia. Subtotal parathyroidectomy is most often performed.
Prognosis and prevention
With timely therapy, renal osteodystrophy can be corrected. The severity of the condition is determined by the stage of renal failure; after kidney transplantation, the prognosis for life is more optimistic. A significant improvement in well–being is observed with subtotal resection of the parathyroid glands – mineralization increases 3-6 months after surgery, bone and joint pain syndrome is stopped within 10 days, muscle strength increases.
Prevention involves the identification of hyperparathyroid states, quitting smoking and alcohol abuse, proper nutrition. Preventive measures for patients on RRT include taking vitamin D after each hemodialysis session. At the first symptoms of trouble from the urinary organs, it is important to immediately contact a urologist or nephrologist, which will allow you to diagnose the pathology at an early stage. Adequate treatment helps to prevent or delay the development of renal insufficiency as much as possible, and consequently osteodystrophy.