Although alterations of different aspects of renal (kidney) function is a frequent complication of multiple myeloma, being reported in 48-77% of cases, the occurence of significant renal dysfunction in this entity is relatively uncommon, occuring in 18-25% of cases. This is due to the fact that only myelomas asociated with high urinary excretion of “light chains” (Bence Jones proteins) carry a definite risk of causing renal damage significant enough to produce complete loss of kidney function and to require renal replacement therapy (hemodialysis). Hence, patients with these types of myelomas should be particularly aware of clinical conditions that may compromise renal function further.
Normal Renal Function:
Each human kidney is composed of approximately one million filtering units known as nephrons. Each nephron consists of a bundle of small capillary blood vessels (the glomerulus) and a set of tubular structures. Urine is produced by filtration of the liquid portion of blood (plasma) at the glomerulus and the subsequent modification of filtrate as it traverses the lumen of the tubules. Normal renal function is important for several reasons:
- to maintain the volume and composition of body fluids;
- to excrete waste products of protein breakdown (mainly urea and creatinine)
- to maintain the red blood cells mass and prevent anemia
- to activate vitamin D and preserve normal bone structure; to maintain the integrity of nerve function
Assessment of Renal Function:
Loss of renal function, referred to as kidney or renal failure, results in an increase in the levels of blood urea and creatinine. Blood urea is usually measured as the levels of BUN (blood urea nitrogen). BUN is a poor index of renal function because its levels are influenced by the content of dietary protein. Creatinine levels, on the other hand, are not affected by diet and are a more accurate index of renal function. As renal function diminishes, the blood concentrations of creatinine rise above the normal range of 0.6-1.2mg/dl. Creatinine concentration is a highly specific but rather insensitive test of renal function, because relatively small changes in creatinine reflect large losses of function. For example, if a patient’s usual creatinine with normal renal function is 0.8mg/dl, a mild increase above normal to 1.6mg/dl reflects a substantial 50% loss of function. The problems of creatinine insensitivity can be circumvented by doing serial, periodic measurements of creatinine or even better by determination of the creatinine clearance. The latter is done by collecting urine for a given time (usually 24 hours) and measuring the creatinine concentration in urine and blood. The normal creatinine clearance ranges from 100-120ml/min. It is essential that urine collection be complete (no skipped samples) and that it be timed accurately.
Alteration of Renal Function:
Impaired renal function is referred to as renal or kidney failure. Unfortunately, clinical symptoms of renal failure occur only after substantial loss of renal function has occured; usually 85-90% functional loss. Thus, a patient may have lost 80% of kidney function and feel pretty well. The loss of more than 90% of kidney function is referred to as End-Stage Renal Failure and requires the institution of dialysis therapy. Therefore, it is essential to recognize the presence of renal failure BEFORE symptoms of renal failure occur and to institute measures to prevent additional loss of function and progression to End-Stage Renal Failure. In practice, ocurrence of renal failure can be recognized early by serial determinations of blood creatinine and the creatinine clearance.
Renal Failure in Multiple Myeloma:
The presence of “light chains” in urine places the patient with multiple myeloma at a high risk of developing renal failure. The risk of renal failure is related mainly to two factors.
- The tumor mass burden: 15-20% incidence in IIB (intermediate tumor mass) and 72-82% incidence in IIIB (high tumor mass).
- The amount of “light chains” in urine: 39% incidence with >2g/day of urine “light chains”, 17% incidence with 0.05-2g/day and 7% incidence with <0.05g/day.
There are other factors that may cause and/or precipitaterenal failure in patients with multiple myeloma, particularly in those with urinary “light chains”.
- Dehydration: occurs when fluid intake is curtailed (because of sickness, nausea, vomiting) or when there is excessive fluid loss (because of vomiting, diarrhea, fever, or excessive sweating).
- Hypercalcemia: approximately 25% of myeloma patients develop hylercalcemia (blood levels above 11mg/dl) due to skeletal breakdown by a myeloma protein (Osteoclast Activating Factor).
- Hyperuricemia: rapid rise in uric acid levels may occur with dehydration or during chemotherapy. The latter may be prevented by treatment with allopurinol.
- Non-Steroidal Anit-Inflammatory Drugs: several of these products are sold over the counter (i.e. Aspirin, Ibuprofen, Advil, Aleve). These should never be used, especially by those with “light chain” myeloma.
- Intravenous Contrast Dye (used for X-ray, IVP, CT scans): Although the risk of developing renal failure may be reduced by adequate hydration, the use of contrast dyes should be avoided. Contrast materials used in nuclear medicine or magnetic resonance scans do not increase the risk of renal failure.
- Infections: any infections, particularly urinary tract infections, may augment the risk of developing renal failure.
There are two types of renal failure in multiple myeloma:
- Acute Renal Failure is a rapid loss of renal function, occuring in days. It may be the initial presentation of multiple myeloma. It may be due to clogging of the renal tubular lumens with plugs (casts) containing “light chains” (“Cast Nephropathy” or “Myeloma Kidney”) and/or some of the factors outlined previously. Acute renal failure may be reversible – kidney function may improve.
- Chronic Renal Failure is a slow, progressive loss of renal function, occuring over weeks or months, that can be recognized by a slow, progressive rise of creatinine blood levels and a decline in creatinine clearance. It is often irreversible (renal function may not improve). It is usually due to Cast Nephropathy or amyloidosis (deposition of abnormal “light chain” related amyloid protein). In amyloidosis, the urine contains large quantities of albumin and the patient blood levels of albumin are markedly decreased. This causes fluid retention and swelling (edema).
Questions to Ask Your Doctor:
- What is my base-line creatinine?
- Is my creatinine rising?
- Do I have “light chain” (Bence Jones) proteins in my urine? If so, have they been quantitated?
- Is my calcium level normal?
- (if chemotherapy is given) Are precautions being taken to prevent increases in uric acid?
- (if X-rays that require IV contrast material are indicated) Are my kidneys at risk of injury? If so, are there alternative ways ofobtaining information required?
- (if new medication is prescribed) Is there a risk of injury to my kidneys?
Minimize Risk of Renal Injury:
To minimize risk of renal injury, multiple myeloma patients should AVOID:
- Dehydration. If fluid intake is curtailed or excessive fluid losses occur, consider having intravenous fluid administered. Monitor your weight regularly – abrupt weight loss means dehydration
- Non-Steroidal Anit-Inflammatory Drugs: Be aware of over the counter medications. Ask your physician about the potential for kidney injury of any medication taken.
Editor’s Note: Dr. Rodriguez is Associate Clinical Professor of Medicine at UCLA and Medical Director of Dialysis Services at Gambro Health Care/Cedars-Sinai Medical Center. He has been a faculty member at IMF Patient & Family Seminars.