Kidney Matters Issue 13 - Summer 2021

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16Kidney ClinicHearts and bones: CKD-MBDChronic kidney disease-mineral bonedisease (CKD-MBD) is very common inpeople with kidney failure, especially ifthey are on dialysis. Definitive diagnosisis surprisingly difficult, and treatmentmust be individualised to each patient’sneeds and preferences.Bone is made of collagen, a protein that provides asoft framework, and calcium phosphate, a mineral thatadds strength and hardens the framework. In healthypeople, nearly all (more than 99%) of the body’scalcium is contained in the bones and teeth.There are two types of bone: cortical and trabecular.Cortical bone is dense and compact and forms therigid outer layer. Trabecular bone forms the inner layerand has a honeycomb-like structure. Cortical andtrabecular bone gives the skeleton the strength andflexibility to withstand stress and resist fracture.Bone is a living, growing structure that constantlychanges as worn-out bone is broken down andreplaced by new bone—called turnover or remodelling.Since the kidneys play an important role in boneremodelling, kidney disease upsets the delicatebalance of minerals in the bones and blood, resultingin hormonal imbalances that lead to CKD-MBD.What is CKD-MBD?As Dr Colin Geddes explains: “The primary role ofthe kidney is to maintain the correct amount andcomposition of the fluid that bathes our cells (theextracellular fluid). Calcium and phosphate are twovery important minerals that have to be controlledin that fluid. It is essential that the level of calcium inthe fluid is kept in a narrow range (2.2-2.6 mmol/L); ifnot, our heart, nerves and muscles cannot functionproperly.” Colin is a Consultant Nephrologist at NHSGreater Glasgow and Clyde.The kidney controls the amount of calcium that passesfrom food into the bloodstream by activating vitaminD, a hormone that is mostly produced in the skin inresponse to sunlight. When the calcium levels in theextracellular fluid and bloodstream fall—for example,if we have not eaten any calcium-containing food—thislow level is detected by the parathyroid glands in theneck, which release parathyroid hormone (PTH).“The worse the kidneyfunction and the lowerthe eGFR, the greater thelikelihood of CKD-MBD“In response to rising PTH, the body breaks down boneto release calcium into the bloodstream and raisethe calcium level back to normal range. When we eatcalcium-containing food, calcium is absorbed backinto the bone, levels of PTH fall, and things are back tonormal.“That is what happens with healthy kidneys. Whenyou have reduced kidney function, especially whenyour kidneys have failed completely and you are ondialysis, your kidneys do not activate vitamin D. As aresult, the calcium level in your blood tends to be low,so your parathyroid glands are permanently overactive(secondary hyperparathyroidism) leading to a highlevel of PTH in the blood. The result is damage to thestructure of the bones and abnormal deposits ofcalcium in the blood vessels and sometimes the jointsand the skin, which is why the condition is called CKD-MBD (see Table),” explains Colin.www.kidneycareuk.org
17Defining CKD-MBDGuidelines for doctors define CKD-MBD as systemicdisorder of mineral and bone metabolism due toCKD manifested by one or a combination of:• Abnormalities of calcium, phosphorus,parathyroid hormone, or vitamin D metabolism• Or abnormalities in bone turnover, mineralisation,volume, linear growth, or strength• Or vascular or other soft-tissue calcification.How common is CKD-MBD?The abnormalities in blood levels of calcium,phosphate and PTH that characterise CKD-MBD arepresent in virtually everyone who is on dialysis. CKD-MBD tends to develop when eGFR is less than 30ml/min/1.73 2 (CKD stage 4), although subtle abnormalitiescan be detected at earlier CKD stages. Generally, theworse the kidney function and the lower the eGFR, thegreater the likelihood of CKD-MBD.CKD-MBD is not the same as osteoporosis, anotherslowly developing condition that affects the structureand strength of the bones. Osteoporosis is causedby age-related changes in bone remodelling, in whichbreakdown of old bone outpaces formation of newbone. Osteoporosis affects both women and men,but women have a higher risk due to loss of oestrogenhormone at the menopause.“Kidney patients have the same risk factors forosteoporosis as the rest of the population, so it ispossible to have both CKD-MBD and osteoporosis—for example, if you are a post-menopausal woman ondialysis. It can be difficult to differentiate betweenthe two conditions, and most kidney specialists findCKD-MBD challenging to diagnose definitively. Thisis because our current tests to monitor and assessCKD-MBD do not give us the full picture of what ishappening to the bones and the blood vessels,“comments Colin.How do I know that I have CKD-MBD?Subtle changes that indicate CKD-MBD can bedetected on X-ray. However, routine X-rays are notrecommended, because they subject people tounnecessary radiation and the results are unlikely tochange treatment.The gold-standard investigation to confirm CKD-MBDis a bone biopsy, in which a doctor uses a specialneedle under X-ray guidance to take small sample ofbone for examination under microscope. However,bone biopsy is rarely used to diagnose and monitorCKD-MBD because it is invasive and potentially painful,and is again unlikely to affect the choice of treatment.Colin adds: “Other possible indications of CKD-MBD arecomplications such as bone pain, low-impact fractures,muscle aches and pains, calcium deposits in the bloodvessels that can reduce the blood supply to that partof the body including the blood vessels around theheart (coronary arteries), calcium deposits on heart
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Kidney Matters Issue 13 - Summer 2021

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