CKD mineral and bone disorder: phosphate retention and secondary hyperparathyroidism
In advanced chronic kidney disease (CKD), the kidneys retain phosphate and make less active vitamin D, so calcium falls and the glands that release parathyroid hormone (PTH) overwork, weakening bone.
Remember
Phosphate up, calcium down, PTH up: in advanced CKD, low calcium with a high PTH points to secondary hyperparathyroidism, where healthy parathyroid glands overwork in response to a problem elsewhere, unlike primary disease where the calcium is high.
Memory aid
the kidneys fail, phosphate piles up, calcium drops, and PTH shouts louder to pull calcium out of bone
Use it to recall the order of events from failing kidneys to raised PTH.
Healthy kidneys clear excess phosphate by passing it into the urine. As chronic kidney disease advances they excrete less, so phosphate builds up in the blood (hyperphosphataemia). The extra phosphate binds free calcium, which lowers the usable calcium level.
The failing kidneys also make less calcitriol, the active form of vitamin D, because the final activation step takes place in the kidney. Less calcium is then absorbed from the gut, so blood calcium falls.
Low calcium and high phosphate both stimulate the parathyroid glands (small glands in the neck that release parathyroid hormone, PTH), so they release more PTH. This is secondary hyperparathyroidism: the glands are healthy and are reacting to a problem elsewhere. In primary hyperparathyroidism a gland itself overproduces PTH, and the calcium is high.
PTH pulls calcium out of bone by stimulating osteoclasts (the cells that break bone down). In the usual high-turnover pattern, bone is broken down faster than it is rebuilt, so the skeleton weakens and bone pain follows. The abnormal bone structure caused by kidney failure is called renal osteodystrophy. Low vitamin D and low calcium are also linked with proximal muscle weakness, which shows as difficulty rising from a chair or climbing stairs.
Typical blood results are low calcium, high phosphate and high PTH, with low active vitamin D and a raised alkaline phosphatase (an enzyme that rises when bone turnover, the constant cycle of breakdown and rebuilding, is high). Treatment lowers phosphate intake and uses phosphate binders (medicines that bind phosphate in the gut) and active vitamin D.
Key facts
- Phosphate
- with failing kidneys less is excreted, so the serum level rises.
- Calcium
- extra phosphate binds free calcium, and active vitamin D falls, so less calcium is absorbed and there is a tendency to low blood calcium.
- PTH
- healthy parathyroid glands release more of it in response, which is secondary hyperparathyroidism.
- Early results
- an early normal phosphate or calcium result does not rule the process out, because PTH can rise first.
- Primary versus secondary
- in primary disease the gland itself overproduces PTH, with a high calcium; in secondary disease the glands are healthy and react to a low calcium.
- Bone patterns
- renal osteodystrophy is usually a high-turnover bone disease driven by hyperparathyroidism, although low-turnover disease and osteomalacia (soft bone from poor mineralisation) also occur.
- Treatment
- cut dietary phosphate, and give phosphate binders and active vitamin D.
Exam traps
- Primary hyperparathyroidism from a parathyroid adenoma (a benign tumour) starts in the gland itself and does not depend on kidney failure. In CKD the glands are overactive in response to low active vitamin D, low calcium and phosphate retention, so the condition is called secondary.
- Hypercalcaemia (a high blood calcium) would not trigger secondary hyperparathyroidism, because high calcium switches PTH release off, not on. In CKD the calcium is typically low.
- More vitamin D activation by the kidney has the direction of change backwards: diseased kidneys convert less vitamin D to calcitriol, so activation falls and calcium absorption drops.
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