Renal Impairment in Multiple Myeloma Patients

This assignment delves into the serious issue of renal impairment frequently encountered in patients with multiple myeloma. It highlights the high incidence of kidney problems in these individuals and discusses various contributing factors such as dehydration, hypercalcemia, nephrotoxic drugs, infections, contrast agents, and proteinuria. The importance of early detection and management is emphasized, as well as treatment approaches like high-dose chemotherapy, plasmapheresis, and addressing underlying causes. The document concludes by stressing the significance of effective renal function management alongside myeloma therapy for improved patient outcomes.

Multiple myeloma development into End Stage Renal Disease 1
Multiple myeloma development into End Stage Renal Disease
Student's Name:
Instructor's Name:
Date:

Multiple myeloma development into End Stage Renal Disease 2
Multiple myeloma development into End Stage Renal Disease
Introduction:
Multiple myeloma is typically a condition which involves slow proliferation of clonal B cells in
the immune system of the body (Katagiri, D et al, 2013). Additionally, there is a production of
monoclonal proteins and lesions of lytic bones (Katagiri, D et al, 2013). The incidence of renal
failure and even chronic renal illnesses such as end stage renal disease (ESRD) is much common
in patients of multiple myeloma (Katagiri, D et al, 2013).. Studies have indicated that the
induction of renal disorders is likely dependent on the infusion of light chains in most cases.
Therefore, renal damage in multiple myeloma is predominantly caused due to the anomalies in
the physicochemical characteristics of light chains (Katagiri, D et al, 2013).
Case study and the presentations:
Mrs. Morris is a 67 year-old African Australian woman. She presented to the emergency unit due
to failure in kidney functions. The reports of her routine blood tests with reference from her
physician of the primary care indicated anomalies in the studies of renal functions. She
additionally complained of non-specific and severe pain in her lower back. Mrs. Morris reported
the onset of back pain six months prior to her admission at the hospital. The pain was also faintly
present in the knees and her feet. Thus, Mrs. Morris reported difficulty in functioning in
everyday life. She was diagnosed with degenerative form of osteoarthritis. She had followed
several traditional methods of healing. Her therapeutic measures included physical therapy along
with the use of occasional medicines of non inflammatory steroids. However, the pain in the
lower back has become severe in the patients due to the ineffectiveness of the medication and

Multiple myeloma development into End Stage Renal Disease 3
therapy followed earlier. Thus, Mrs. Morris reported a persistent and severe lower back pain
along with pain in the right knee. Mrs. Morris faced difficulty in mobilization and had to use a
cane for ambulation. Mrs. Morris reported having nausea and vomiting along with severe decline
in appetite about one week before her admission into the hospital. The reports from her blood
tests indicated elevated levels of blood urea nitrogen and concentration of creatinine. These
results suggest abnormality in kidney functionality. Mrs. Morris additionally experienced
subjective fevers of low grade during the nights. However, there was no observable loss in body
weight. Fevers were typically not accompanied by chills or breaks of sweat during the nights.
There was also the absence of typical characteristics such as dysuria, reduced output of urine, or
the occurrence of gross hematuria.
Current and previous medical history:
Her medical history indicated chronic hypertension. She also had mild obesity which contributed
to the hypertension. She was being treated for blood pressure with the medications of
hydrochlorothiazide and benazepril along with nabumetone. She admitted having taken over the
counter drugs for symptom control as they have anti-inflammatory drugs for pain in joints. The
vital signs as observed in the emergency were normal. The physical examination of Mrs. Morris
revealed a mild degree of discomfort along with deep palpitations in the abdomen region. The
patient did not display an incidence of erythema, warmth around the area of the knee, or
effusion. However, the region around the right knee was tender to palpation. The patient did not
show evidence to neuropathy. The tests conducted on the patient indicated the value of 102
mg/dL of blood urea concentration, 14.0 mg/dL of serum creatinine, level of albumin of 3.4
g/dL, and a mild elevation in the level of globulin with a value of 3.9 g/dL. The level of

Multiple myeloma development into End Stage Renal Disease 4
hemoglobin of the patient was at 12.9 g/dL and hematocrit level was at 36% where rouleaux was
absent in the smear. The patient was admitted for abnormal kidney functionality values. The
collected urine sample over a span of 24 hours was tested and revealed 2.6 g of protein along
with 1.1 g of creatinine. The etiology that preceded the kidney failure was quite unclear at the
time of admission due to which the patient was advised to undergo renal biopsy. The biopsy was
studied under light microscopic technique which revealed that there was a presence of large casts
of hyaline which were mononucleate. Additionally, giant cells containing multiple nuclei were
also observed. The kappa staining procedure indicated positive staining of casts of tubular
conformation. The findings of the biopsy reports were congruent with the results of nephropathy
of myeloma casts. Amyloid was absent on the biopsy. The electrophoresis of the serum protein
sample from the showed the presence of a monoclonal spike in the region of gamma along with a
free band of kappa in the gamma region in an immunoelectrophoresis test. The electrophoresis of
urine sample of the patient showed a prominent M spike of 62.1 mg/dL. Multiple lesions of the
osteosclerotic nature were observed in the skull in the radiographic survey of the skeletal system.
Various scattered lesions lytic lesions were present in the right humerus in the proximal position,
the scapula on the right, and bilateral femurs on the distal side. The hematological reports of the
patient indicated the presence of hypercellular organization and diffuse plasmacytosis which
were diffuse in nature. Flow cytometry tests of the biopsy confirmed a population of monoclonal
plasma cells with restriction of kappa cells along with negative ancillary stains.
Pathogenesis of multiple myeloma:
The patient was diagnosed with multiple myeloma of the free light chain containing nephropathy
of the casts. Multiple myeloma is a proliferation of plasma cells in a malignant manner (Kuo, VC

Multiple myeloma development into End Stage Renal Disease 5
et al, 2011). It is a disease of clonal B-cells and is typically characterized by the malignant
proliferation of plasma cells (Katagiri, D et al, 2013). Along with the proliferation event, there is
an accompanied production of monoclonal proteins and lesions of the lytic bones (Katagiri, D et
al, 2013). In most cases of multiple myeloma, the disease develops into severe impairment of the
renal system due to a significant reduction in the clearance of creatinine (Katagiri, D et al, 2013).
Although there is much progress in the regimens in polychemotherapy with a significant
elevation in the rates of response, the median time of survival with conventional practices of
chemotherapy for therapy is within a span of two to three years (Katagiri, D et al, 2013). High
doses of chemotherapy are supported by transplantation of autologous bone marrow and stem
cells of the peripheral blood stream (Chu, P, 2013). It is typically characterized by a neoplastic
proliferation of the cells of the plasma (Chu, P, 2013). In most percentage of cases of multiple
myeloma, the proliferation of plasma cells occurs alongside with the production of
immunoglobulins of a single class (Chu, P, 2013). This class of immunoglobulins is known as a
monoclonal protein or M protein (Chu, P, 2013). The M protein may belong to any particular
class of immunoglobulins such as IgG, IgA, or IgM (Chu, P, 2013). Alternately, the M protein
may belong to a light chain present in the urine or serum (Katagiri, D et al, 2013; Chu, P, 2013).
Impairment of the renal system as a consequence of multiple myeloma is one of the most
common features (Katagiri, D et al, 2013; Chu, P, 2013). Research has indicated that the
impairment of renal function is often associated with survival rates of inferior order (Katagiri, D
et al, 2013; Chu, P, 2013). The presence of hypercalcemia and light chain proteinuria are
considered some of the primary causes of myeloma in a majority of the cases (Katagiri, D et al,
2013; Chu, P, 2013). At the time of diagnosis, the level of serum creatinine of a considerable
percentage of patients having multiple myeloma exceeds the upper limit of the normal range

Multiple myeloma development into End Stage Renal Disease 6
(Katagiri, D et al, 2013; Chu, P, 2013). Additionally, renal impairment occurs in most patients at
a subsequent stage of multiple myeloma (Katagiri, D et al, 2013; Chu, P, 2013). A large number
of the patients develop severe renal impairment with the progression of the disease (Katagiri, D
et al, 2013; Chu, P, 2013). For the effective therapy of these patients, it is crucial to incorporate
novel agents of chemotherapy such as thalidomide and bortezomib as research has shown that
there is a considerable improvement in the condition of the patients having multiple myeloma
(Katagiri, D et al, 2013; Chu, P, 2013). Research has further indicated that there is evidence for
the improvement of patients who have developed renal failure (Katagiri, D et al, 2013; Chu, P,
2013). Certain studies in literature report that the reversal of renal impairment is often associated
with improved rates of survival (Katagiri, D et al, 2013; Chu, P, 2013). Therefore, literature lays
emphasis on complete and effective assessment and initial analysis of myeloma or other related
disorders of the plasma cell including the diseases of IgGs deposition or amyloidosis (Katagiri, D
et al, 2013; Chu, P, 2013). On the converse, disorders of the plasma cell are considered
important in the differential diagnosis of the patients who present with renal failure of either
acute or chronic type (Katagiri, D et al, 2013; Chu, P, 2013).
Multiple myeloma and renal involvement:
In patients of multiple myeloma, one of the most common and typical complications of the renal
function is that of Cast nephropathy (Katagiri, D et al, 2013; Chu, P, 2013). There is sufficient
evidence that the free light chains have a vital role in the causation of the damage to renal
functionality (Katagiri, D et al, 2013; Chu, P, 2013). Most studies have indicated that the
infusion of light chains are typically purified from patients who have renal failure along with
being responsible for the induction of tubular cast nephropathy (Katagiri, D et al, 2013; Chu, P,

Multiple myeloma development into End Stage Renal Disease 7
2013). The occurrence of damage to the renal function is considerably lower in animals which
are treated with light chains obtained from patient samples (Katagiri, D et al, 2013; Chu, P,
2013). However, there is no available evidence of renal disease (Katagiri, D et al, 2013; Chu, P,
2013). There are considerable differences in the physicochemical properties present in the light
chains (Katagiri, D et al, 2013; Chu, P, 2013). In most healthy individuals, the synthesis of
heavy chains and light chains occurs in the B cells along with a slight excess of light chains in
comparison to the heavy chains (Katagiri, D et al, 2013; Chu, P, 2013). Consequently, a regular
filtration of small amounts of various light chains occurs at the glomerulus (Katagiri, D et al,
2013; Chu, P, 2013). A reabsorption of these light chains in the proximal tubuli occurs along
with a catabolization (Katagiri, D et al, 2013; Chu, P, 2013). In cases of multiple myeloma,
there is an increase in the ability of reabsorption and catabolization of the proximal tubular cells
(Katagiri, D et al, 2013; Chu, P, 2013). As a consequence, there is a lack of reabsorption of light
chains in the proximal tubuli (Katagiri, D et al, 2013; Chu, P, 2013). Therefore, the light chains
reach the nephron at its distal segment (Katagiri, D et al, 2013; Chu, P, 2013). In the distal
segment of the nephron, wherein the light chains are able to get combined with the Tam-Horsfall
mucoprotein (THM) along with the occurrence of precipitation that leads to the formation of
casts which are obstructing (Katagiri, D et al, 2013; Chu, P, 2013). This obstruction in the distal
tubuli typically leads to the leakage in the tubular content (Katagiri, D et al, 2013; Chu, P, 2013).
The tubular content leaks into the interstitium which results in the appearance of classic tubular
cast and the kidney with myeloma (Katagiri, D et al, 2013; Chu, P, 2013). More often than not,
the impairment of renal function develops at a rapid rate along with a consistent ratio of
production and concentration of serum in light chains (Katagiri, D et al, 2013; Chu, P, 2013).
There are various factors that catalyze the formation of renal casts in most myeloma patients

Multiple myeloma development into End Stage Renal Disease 8
(Katagiri, D et al, 2013; Chu, P, 2013). The incidence of dehydration in most diuretics along
with reduction in the glomerular filtration rate and also leads to the elevation of the concentration
of light chains in the plasma which ultimately results in the increase in the capacity of
reabsorption and the catabolism of the light chains present in the tubuli of the proximal region
(Katagiri, D et al, 2013; Chu, P, 2013). Hypercalcaemia is likely to induce vasoconstriction
which is followed by a reduction in the glomerular filtration rate (Katagiri, D et al, 2013; Chu, P,
2013). Several medications, particularly non-steroidal anti-inflammatory drugs (NSAIDS) lead
to the decrease in the blood flow in the renal system (Katagiri, D et al, 2013; Chu, P, 2013).
Agents of radiographic contrast lead to the induction of acute renal failure in patients of
myeloma (Katagiri, D et al, 2013; Chu, P, 2013). The renal failure is especially resulted in
patients who have dehydration or the use of media of ionic contrast has been made (Katagiri, D
et al, 2013; Chu, P, 2013).
Renal failure in multiple myeloma – management:
Most patients with multiple myeloma typically experience a certain degree of insufficiency of
renal function (Katagiri, D et al, 2013; Chu, P, 2013). In a majority of the patients, the function
of the renal system is found to improve with measures of rehydration, treatment of conditions of
hypercalcaemia associated with biphosphonates (Katagiri, D et al, 2013; Chu, P, 2013).
Additionally, management of fluid rehydration, administration of glucocorticoids elements, or
even discontinued administration of nephrotoxic drugs including NSAIDs (Katagiri, D et al,
2013; Chu, P, 2013). A considerable number of patients have the ability to recover in the initial
period of six weeks (Katagiri, D et al, 2013; Chu, P, 2013). Recovery at the later stages is
possible in some patients as well wherein myeloma was found to be one of the most common

Multiple myeloma development into End Stage Renal Disease 9
diagnoses in patients who have been able to discontinue long term dialysis (Katagiri, D et al,
2013; Chu, P, 2013). Plasma exchange and method of plasmapheresis have been primarily
proposed as an effective method of prevention of renal failure associated with light chains
(Katagiri, D et al, 2013; Chu, P, 2013). This is achieved by the removal of light chains from the
plasma region (Katagiri, D et al, 2013; Chu, P, 2013). In comparison to the discontinuation of
dialysis, plasma exchange is regarded an effective alternative therapy for the prevention of
progression of acute renal failure to the stage of chronic renal failure or end stage renal disease
(Katagiri, D et al, 2013; Chu, P, 2013). The efficacy of the treatment has been established in
literature (Katagiri, D et al, 2013; Chu, P, 2013). However, its efficacy has been found to be
limited to patients with the syndrome of hyperviscosity (Katagiri, D et al, 2013; Chu, P, 2013).
A prospective study which is randomized and controlled is required for the decision of
recommending the method of plasma exchange (Katagiri, D et al, 2013; Chu, P, 2013). The
determination of plasma treatment procedure as a standard method also depends on the efficacy
on almost all patients, especially for patients with progressive renal failure caused from Bence-
Jones multiple myeloma (Katagiri, D et al, 2013; Chu, P, 2013). The risk of failure of renal
function increases along with the increase in the load of tumor (Katagiri, D et al, 2013; Chu, P,
2013). However, the underlying tumor burden that ultimately leads to the determination of the
rate of survival (Katagiri, D et al, 2013; Chu, P, 2013). Therefore, the treatment of myeloma for
the achievement of remission that can likely lead to the reduction of the incidence of
insufficiency of renal function (Katagiri, D et al, 2013; Chu, P, 2013). The standard method of
treatment of the treatment of the overt symptomatic disease is the method of chemotherapy for
the melphalan and prednisone (Katagiri, D et al, 2013; Chu, P, 2013). Research indicates that
when chemotherapy is increased to five times the standard dosage, the rate of remission is also

Multiple myeloma development into End Stage Renal Disease 10
increased considerably (Katagiri, D et al, 2013; Chu, P, 2013). The transplantation of the
haematopoeitic stem cells have been found to lead to the reduction in the rate of death related to
treatment (Katagiri, D et al, 2013; Chu, P, 2013). Several randomized control studies indicate
that the rates of remission along with improved rates of survival following treatments of high
dosage with transplantation with haematopoeitic stem cells (Katagiri, D et al, 2013; Chu, P,
2013). Literature indicates that melphalan is the most suitable agent for chemotherapy of high
dosage (Katagiri, D et al, 2013; Chu, P, 2013). The patients with multiple myeloma induced
renal failure showed great improvement in the rate of remission with the use of high dose
chemotherapy (Katagiri, D et al, 2013; Chu, P, 2013). Certain studies have revealed that the
therapy of high dose chemotherapy is effective in patients of all age groups, even up to the age of
eighty (Katagiri, D et al, 2013; Chu, P, 2013). However, in literature, there is an indication that
high dosages of melphalan can lead to induction of renal failure (Katagiri, D et al, 2013; Chu, P,
2013). Severe mucositis may also be resulted from high doses of melphalan and thus, it should
be reduced (Katagiri, D et al, 2013; Chu, P, 2013). Supportive therapies including
biophosphonates are known as inhibitors of considerable potency for bone resorption (Katagiri,
D et al, 2013; Chu, P, 2013). In patients with multiple myeloma are used primarily for treatment
of hypercalcaemia (Katagiri, D et al, 2013; Chu, P, 2013).
Conclusion:
For patients of multiple myeloma, the likelihood of incidence of renal impairment is high
(Katagiri, D et al, 2013; Chu, P, 2013). Therefore, at the time of diagnosis of multiple myeloma,
renal impairment has to be anticipated. In patients with multiple myeloma, cast nephropathy
accompanied by renal failure is typically increased by the depletion of volume, hypercalcaemia,

Multiple myeloma development into End Stage Renal Disease 11
administration of drugs of nephrotoxicity, infection, or agents of contrast, and proteinuria
(Katagiri, D et al, 2013; Chu, P, 2013). In the aged patients of multiple myeloma the
identification of unrelated causative factors for the impairment of renal function including
renovascular disease or prostratic obstruction (Katagiri, D et al, 2013; Chu, P, 2013). Since the
rate of mortality of patients with multiple myeloma induced renal failure is considerably high,
the early diagnosis and prevention is important (Katagiri, D et al, 2013; Chu, P, 2013). Rapid
and immediate removal of light chains with high dose chemotherapy or plasmapheresis is
extremely important for the prevention of irreversible failure or renal function or reduction in the
risk of damage of renal function (Katagiri, D et al, 2013; Chu, P, 2013). The crucial factors that
affect the renal function include the degree of failure of renal function, incidence of
hypercalcaemia, and excreted amounts of protein (Katagiri, D et al, 2013; Chu, P, 2013). The
effective treatment of failure of renal function along with myeloma therapy leads to the reduction
of adverse events with prolonged rates of survival.

Multiple myeloma development into End Stage Renal Disease 12
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