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Multiple Myeloma Symptom, Side Effect- Renal Insufficiency, Kidney Failure

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“Renal failure (kidney damage) represents the most important factor influencing survival in patients with multiple myeloma…”

Once again, I am writing about both a multiple myeloma symptom, as well as a multiple myeloma side effect. Multiple myeloma itself can produce light chain proteins that can cause renal insufficiency. If the damage to the kidneys is severe enough, light chain proteins can cause chronic kidney disease and failure.

The question is, do MM patients die of chronic kidney failure only because of multiple myeloma light chains or do MM therapies add to kidney disease in MM patients causing renal insufficiency to become chronic kidney disease, the second leading cause of death in multiple myeloma?

 

Renal Disease in Multiple Myeloma- symptom-

When kidney damage is caused my multiple myeloma itself:

According to the American Society of Nephrology:

  • Renal insufficiency (serum creatinine of >1.3 mg/dl) is found at presentation in almost 50% of newly diagnosed MM patients-
  • Severe renal insufficiency (serum creatinine >2.0 to 2.5 mg/dl) is seen in >15 to 20% of cases-
  • Proteinuria is observed in >80% of MM cases-
  • Fewer than 15 to 25% of patients with myeloma actually develop the nephrotic syndrome-

Renal Disease in Multiple Myeloma- side effect-

When kidney damage is man-made or what I consider to be a side effect of external factors, kidney  damage can be caused by:

  • Chemotherapy, “Many medicines that treat tumors are removed from the body by the kidneys and can damage certain cells within the kidneys…”
  • Bisphophonates, “Preclinical studies have demonstrated distinct differences among bisphosphonates in the risk for histopathologic renal damage and the potential to cause cumulative toxicity over time [15, 16]”
  • Radiocontrast agents,Contrast-Induced Nephropathy has been reported to be the third leading cause of acute kidney injury (AKI) in hospitalized patients in the United States (behind pre-renal kidney injury and nephrotoxic medications)…”
  • Nonsteroidal anti-inflammatory drugs,NSAIDs can induce several different forms of kidney injury including hemodynamically mediated acute kidney injury…”

Complicating long-term MM survival with kidney damage further, is the idea outlined in the top study linked below,  that clinical research of side effects caused by chemotherapy regimens may be subjective.

If you are a newly diagnosed MM patient the overwhelming odds are that your kidney function is being damaged by your multiple myeloma. The degree of this damage is based on many factors.  Each relapse will cause your MM to cause more kidney damage.

The focus of this post is to raise the issue that the

  • chemotherapy,
  • bisphosphonate therapy,
  • contrast agents and
  • NSAIDS

that you undergo will, according to research, cause more damage to your kidneys.

Is it possible that kidney damage caused year after year (assuming the 5-7 year average MM survival) could push you to kidney failure? I think this is probable…

Is that multiple myeloma patients struggle to manage their incurable blood cancer at the expense of their kidney health? To put this another way, aggressive MM therapy such as chemo and bisphosphonates can manage a patient’s MM while damaging his/her kidney health.

Please understand that I am not placing the onus of maintaining kidney health only on standard-of-care MM therapies. I’m saying that MM itself can cause kidney damage. To add man-made therapies that cause further kidney damage may be the reason why kidney failure is the second most common cause of death for MM patients and survivors.

The possible solutions? First, it is in the long-term interest for every newly diagnosed MM patient to be aware that both MM as well as MM therapies cause ongoing damage to their kidneys…for the rest of their lives.

Second, evidence-based but non-toxic, non-conventional kidney therapies shown to heal kidney function. Nutrition, supplementation and lifestyle therapies shown to improve kidney health.

For more information about evidence-based but non-toxic kidney therapies, please scroll down the page, post a question or comment and I will reply to you ASAP.

Hang in there.

David Emerson

  • MM Survivor
  • MM Coach
  • Director PeopleBeatingCancer

Recommended Reading:


Variation in how side effects are reported clouds drug safety

“A new study finds significant variation in how drug side effects are reported, potentially making some drugs seem safer or less safe than they really are

“Without standardizing how we present such data, there is the potential for misinformation about these side effects…”

“Determining if a side effect is treatment-related or not is subjective. If you rely on this, you get rid of some of the background noise of coincidental symptoms. However, you can also miss more subtle side effects…”

Light Chain-Associated Renal Disorders

“Light chains are divided into 2 major classes based on the amino acid sequence in the constant portion of the polypeptide chain and are designated as kappa and lambda…

Prognosis-

Overall, the prognosis depends on the type and extent of the underlying condition. Renal failure is much more prevalent in patients with light-chain proteinuria, and the severity of the renal failure correlates with the light-chain protein excretion rate. Acute renal failure is observed less frequently (8-30%), while chronic kidney disease is quite common (30-60%)…

Renal insufficiency may be indolent, chronic and progressive, or rapidly progressive. Renal insufficiency, a common manifestation of multiple myeloma, is present in more than 50% of patients. [8] …

Myeloma kidney (cast nephropathy)-

More than 50% of patients with multiple myeloma die from renal failure, and a large number of these deaths are erroneously attributed to so-called myeloma kidney. However, myeloma kidney is only one of the several causes of renal dysfunction in patients with multiple myeloma, in which specifically proteinaceous casts are observed obstructing the distal tubules and collecting ducts.

Multiple myeloma-

Infections and renal failure are the major causes of death in patients with multiple myeloma. Renal failure represents the most important factor influencing survival in patients with multiple myeloma.

Despite aggressive therapy, patients with renal failure and myeloma have a considerably worse prognosis compared to those with myeloma who do not have renal insufficiency. [8]  The prevalence rates for renal failure are also related to the type of myeloma, ie, 14% of patients with IgG myeloma, 33% of those with IgA myeloma, and 60% of individuals with IgD myeloma have renal failure.

The prevalence rates for renal failure are also related to the type of myeloma, ie,

  • 14% of patients with IgG myeloma,
  • 33% of those with IgA myeloma, and
  • 60% of individuals with IgD myeloma

have renal failure…

Once renal insufficiency is present, the relationship between the degree of renal impairment and the duration of survival is dramatic.

  • With a serum creatinine level of less than 120 µmol/L (1.4 mg/dL), median survival is 44 months.
  • With a serum creatinine level of 120-180 µmol/L (1.4-2 mg/dL), median survival is 18 months.<
  • With a serum creatinine level greater than 180 µmol/L (>2 mg/dL), median survival is 4.3 months.

Patient Education-

Instruct patients to maintain adequate hydration, with a daily oral fluid intake of 2-3 liters, unless fluid restriction is needed because of advanced renal failure.

Warn patients to avoid anti-inflammatory agents (NSAIDS) because these aggravate renal dysfunction and may precipitate acute renal failure.

Educate patients about the risk of contrast agents that may precipitate kidney failure. They should question the necessity of a contrast imaging study and request alternative studies, if available.

Serum free-light chain (FLC, Freelite) assay

Most cases of myeloma cast nephropathy occur in patients with serum FLCs above 100 mg/dL, and FLCs less than 70 mg/dL are rarely observed. [13]…

Plasmapheresis-

The strong association between light-chain excretion and renal failure suggests that light chains play a primary pathogenetic role in producing kidney damage. Plasma exchange appears to be the most efficient way to rapidly remove large amounts of light chains and has been advocated by many over the last 15 years, but its efficacy has not been established convincingly

Early and aggressive therapy with 5-7 exchanges within 7-10 days is recommended, and the duration of therapy should be guided by serum free light chains with the aim to reduce light chains by a minimum of 60% for recovery of renal function. [26] Plasmapheresis should be performed in conjunction with dexamethasone and bortezomib-based chemotherapy to reduce light chain production…

Prevention-

Maintain adequate fluid intake (2-3 L/d), especially before initiating chemotherapy, to prevent dehydration.  Dehydration and aciduria favors precipitation of light chains. This is important in the precipitation of acute renal failure in a significant number (up to 95%) of patients.

Avoid nephrotoxic agents. NSAIDs, often used to relieve bone pain, are the most prominent offenders.

Ensure early and effective treatment of infections with nonnephrotoxic antibiotics.

Early recognition and treatment of hypercalcemia are important. Excessive calcium is an important cause of acute renal failure in patients with myeloma and may be present in up to 30% of patients…

Medication Summary

No standard treatment has been established for light-chain nephropathy, and the mainstay remains treatment of the underlying disease process and monitoring for complications and early recognition and management of complications.

In patients with myeloma, prevention of cast nephropathy is the mainstay by reducing the production of light chains by dexamethasone-based chemotherapy and promoting light chain filtration by optimizing volume status and intravenous fluid therapy to maintain urine volume of approximately 3 L/day, unless contraindicated, and alkalization of urine…

Bortezomib-based chemotherapy, in addition to early plasmapheresis, in patients with multiple myeloma and kidney failure secondary to myeloma cast nephropathy has shown to achieve complete renal recovery in 40% of patients and is preferred therapy in this subset of patients… [18]

 

 

 

 

 

 

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