Renal osteodystrophy

Description:

Renal osteodystrophy - damage of a skeleton owing to HPN. The main histologic changes at a renal osteodystrophy can be caused:
the secondary hyperparathyreosis (the strengthened bone metabolism, fibrous osteit) resulting from a hyperphosphatemia, a hypocalcemia, calcitriol synthesis suppression (the 1,25-diguide-roksivitamina of D) and nonsensitivities of skeletal fabric to parathyroid hormone;
the lowered bone metabolism (osteomalacy and aplasia of bones) most often arising owing to an aluminum delay in an organism at reception of the means connecting phosphate which part aluminum is, and at treatment by a hemodialysis;
combination of the specified reasons (the mixed renal osteodystrophy).

Reasons of a renal osteodystrophy:

At depression of function of kidneys harmonious regulation of phosphorus-calcium exchange is broken, the secondary hyperparathyreosis develops. Key pathogenetic factors of formation of VGPT and POD as its main manifestation, are:

- disturbance of synthesis and effect of calcitriol (C);

- phosphate delay;

- decrease (or decrease threat) concentration of calcium in extracellular liquid;

- the pathological answer of epithelial bodies to concentration of calcium in extracellular liquid;

- disturbance of effect of parathormone (PTG)

Reduction of renal synthesis of C happens already at an initial stage of a renal failure. The reasons of it are decrease of the activity of a 1a-hydroxylase of proximal tubules of kidneys, and also a hyperphosphatemia. Decrease in the C level leads to increase in concentration of PTG, it occurs already at clearance of creatinine of 60 ml/min. The number of receptors to C in epithelial bodies decreases. As a result the suppressive effect of C on synthesis and secretion of PTG weakens and there is a resistance of a skeleton to its kaltsiyemichesky action that strengthens PTG hypersecretion. Deficit of C reduces absorption of calcium (Са) in intestines, conducts to a hypocalcemia which in addition stimulates development of PTG. The raised products of PTG in response to a system hypocalcemia are mediated by receptors of Sa. At development of VGPT the expression of receptors of Sa decreases, there is also a decrease in an expression of receptors of vitamin D that in addition reduces a possibility of Sa and C to regulate secretion of PTG.

At most of patients with an end-stage of HBP the hyperphosphatemia as intake of phosphates with food exceeds possibilities of their elimination during dialysis which is traditionally carried out 3 times a week develops. Inadequately treated hyperphosphatemia plays an important role in progressing of HBP, development of VGPT and POD:

- directly stimulates synthesis of PTG with epithelial bodies;

- leads to reciprocal decrease in calcium ions in blood that strengthens the available hypocalcemia;

- inhibits calcitriol synthesis;

- causes development of resistance of receptors of calcitriol to its action;

- leads to decrease in number of receptors of Sa by means of which Sa can stimulate synthesis of calcitriol in kidneys;

- inhibits a 1a-hydroxylase which is carrying out synthesis of an active form of vitamin D.

Besides, the hyperphosphatemia is the independent factor increasing mortality of dialysis patients. The mechanism of increase in mortality is definitely not installed probably it results from strengthening of cardiovascular calcification.

As PTG influences the cellular alarm system which is present practically at all cells and body tissues, in addition to the known disturbances of calcium-phosphorus metabolism, through Sa-zavisimye mechanisms this hormone exerts impact on functions of many bodies and systems, causing pleyotropny organ dysfunction at uraemia. VGPT promotes, in addition to development UNDER, to formation of an uraemic cardiomyopathy, calcification of a myocardium, valves of heart and the carrying-out system, extra skeletal calcification, arterial hypertension, atherosclerosis, a vasculopathy, encephalopathy, influences practically all cells of a hemogenesis, insulin secretion disturbance. All these disturbances practically do not react to dialysis therapy, but are inseparably linked, at least partially, with PTG hypersecretion.

At it is long the existing secondary hyperparathyreosis the hyperplasia of epithelial bodies with formation of independently functioning adenomas of epithelial bodies develops – it the state is called a tertiary hyperparathyreosis.

Symptoms of a renal osteodystrophy:

Clinical picture UNDER has some distinctions depending on its form described further manifestations in the greatest measure are characteristic of a fibrous osteit.

Development of a skin itch which can carry both constant, and periodic character is characteristic. Patients complain of ostealgias, joints. Calcium can be laid in a cartilage, then elastic properties of a joint are broken. There can be deposits in ligaments and sinews. "duck gait" in connection with the listed changes in bones is characteristic. Calcium can be laid subcutaneously, forming kaltsinata of soft tissues. Calcification of vessels, including hypodermic, leads to development of the centers of a necrosis of skin (kaltsifilaksiya).

Due to the disturbance of processes of neuromuscular transmission muscular weakness which progresses develops, taking upper extremities. Changes from the central nervous system are characteristic: block, drowsiness, decrease in memory. The gastrointestinal tract disease includes development of a persistent peptic ulcer of a stomach and the duodenum which is not giving in to treatment by usual drugs, chronic pancreatitis.

Carry fractures of bones, ruptures of sinews, a pancreatonecrosis, focal changes of a myocardium (clinic of a heart attack), arrhythmias, and also acute giperkaltsiyemichesky crisis to complications of VGPT. It is the urgentny situation developing at calcium level more than 3,5 nmol/l. Patients complain of sharp weakness, appetite reduction, confusion of consciousness, symptoms of an acute abdomen, a polyuria, vomiting, thirst (as result of dehydration). On an ECG: lengthening of an interval of RO, arrhythmia, blockade.

Clinical features UNDER with low exchange of a bone are early heavy anemia, it is frequent – resistant to erythropoetin drugs, and also higher risk of emergence of ekstrakostny calcificats as a result of a persistent hypercalcemia as consequences of reduced ability of a bone tissue to accumulate Sa.

Treatment of a renal osteodystrophy:

Correction of disturbances of phosphorus-calcium exchange and VGPT depend on a stage of HBP, weight of VGPT, emergence of side effects. Today the main stages of prevention and treatment of a renal osteodystrophy is the following:

- correction of a hyperphosphatemia;

- treatment by vitamin D drugs;

- parathyroidectomy.

Correction of a hyperphosphatemia plays an important role in prevention and treatment UNDER. As consumption of phosphates with food averages 900-1200 mg/days, and removal at dialysis – 250-300 mg for the procedure, it is obvious that patients on dialysis have an inevitable positive balance of phosphates. On the one hand, the hyperphosphatemia is one of the reasons of formation of a hyperparathyreosis as POD leading pathogenetic substrate. On the other hand, the hyperphosphatemia is the independent factor increasing mortality of dialysis patients, presumably, in connection with acceleration of cardiovascular calcification. Actions for correction of a hyperphosphatemia include a hypophosphatic diet, use phosphate-binderov, increase in efficiency of dialysis.

Most often in quality phosphate-bindera is used calcium a carbonate or calcium acetate inside on average 2-3 grams a day. The maximum dose – 10 g/days, however in practice гр / days do not appoint more than 6. The daily dose is divided into 3 receptions which carry out in intervals between food.

At inefficiency of a diet and use phosphate-binderov dialysis intensification which can be reached in several ways is shown:

- increase in surface area of a dialyzing membrane, for example, from 1 sq.m to 2 sq.m;

- increase in time of dialysis, for example from 4 h 3 times a week to 5-6 h 3 times a week;

- increase in number of sessions of dialysis in a week with 3 to 4-6.

Treatment by vitamin D drugs. An effective therapeutic method is purpose of active derivatives of vitamin D: calcitriol, альфакальцидол. This method with success is applied in world nephrological practice since 1984 and today is a basis of conservative therapy of VGPT at dialysis patients. Discovery of the direct inhibiting effect of C on synthesis of PTG strengthened positions of this method of treatment even more.

Indications to purpose of drugs of vitamin D, include:

1) replacement therapy for the purpose of prevention of development of a secondary hyperparathyreosis; 2) suppressive therapy at already developed hyperparathyreosis. Supressivny therapy by drugs C, according to recommendations of K/DOQI, is shown at increase in the PTG level> 300 ¡ú/l. The Russian authors suggest to appoint active metabolites of vitamin to D patients with HBP end-stage according to the following indications:

- increase in the PTG level more than 200 ¡ú/l;

- increase in kShchF and osteocalcine at the PTG 120-200 level ¡ú/l;

- a persistent hypocalcemia at effective correction of a hyperphosphatemia.

Replacement therapy assumes use of small doses of C (0,125-0,25mkg in days) whereas for treatment high doses are used considerably.