26th June 2023

Malignancy and the kidney

Solid tumours

The kidney is affected by many different malignant diseases, by direct involvement of the kidneys, or indirectly by involvement of other parts of the urinary tract. The most common cause of this is obstruction from either a primary tumour or metastasis, resulting in a post-renal acute kidney injury. These tumours can include primary renal adenocarcinoma, tumours of the urothelium or bladder, or the cervix. Glomerulonephritis can also occur as a result of an immunological reaction to other tumours or also as a result of a paraneoplastic syndrome.

Hypercalcemia can occur as a paraneoplastic syndrome from a solid tumour. This frequently happens in breast cancer and lung cancer, caused by parathyroid hormone related protein (PTHrP) or secondary to bone metastasis. High levels of calcium can lead to renal complications, such as renal calculi. The acute drop of the glomerular filtration rate that also occurs as a result of hypercalcaemia is thought to be mediated by renal vasculature constriction in response to the high calcium, leading to a reduced glomerular blood flow and filtration. Hypercalcaemia is also associated with increased sodium excretion and water excretion.

Sometimes treatment of leukaemia and lymphoma, or the resultant tumour lysis syndrome with allopurinol, can be complicated by acute interstitial nephritis. Hypercalcemia caused by the release of calcium in tumour lysis syndrome can also occur in this context, as well as in plasma cell tumours such as myeloma.

Myeloma

In myeloma and other monoclonal gammopathies, renal impairment occurs as the result of the nephrotoxic effect of immunoglobulin light chains. Multiple myeloma is a malignant proliferation of plasma cells. Normal plasma cells come from the B cell line and produce immunoglobulins. Normal immunoglobulins are polyclonal composed of a variety of heavy chains and light chains. In myeloma, plasma cells produce immunoglobulin of a single heavy and light chain, known as a monoclonal protein or paraprotein. The most well-known of these, which occurs in the urine, is known as the Bence Jones protein, which occurs when only a light chain is produced.

Diagnosis of myeloma requires two of the following criteria:

1. Increased malignant plasma cells in the bone marrow (>10%)
2. Serum or urinary paraprotein
3. A myeloma defining event (remembered by the mnemonic CRAB):
   • C – Calcium: hypercalcaemia
   • R – Renal: Renal involvement
   • A – Anaemia: low Hb
   • B – Bone: lytic bone lesions

End organ damage can occur in myeloma, with the kidneys, bone marrow or bones themselves being more susceptible. Renal failure can occur due to paraprotein deposition, hypercalcemia, an increased susceptibility to infection or amyloidosis. Treatment is often with intravenous fluids to treat the renal impairment and is the first line treatment for hypercalcemia caused by multiple myeloma.