Multiple Myeloma Development into End Stage Renal Disease

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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 therapy followed earlier. Thus, Mrs. This report is prepared in order to gain good knowledge and understanding the concepts while writing an assignment work on particular topic. 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.

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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 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 [1]. It is a disease of clonal B-cells and is typically characterized by the malignant proliferation of plasma cells Along with the proliferation event, there is an accompanied production of monoclonal proteins and lesions of the lytic bones 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 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 High doses of chemotherapy are supported by transplantation of autologous bone marrow and stem cells of the peripheral blood stream . It is typically characterized by a neoplastic proliferation of the cells of the plasma. In most percentage of cases of multiple myeloma, the proliferation of plasma cells occurs alongside with the production of immunoglobulins of a single class. This class of immunoglobulins is known as a monoclonal protein or M protein . The M protein may belong to any particular class of immunoglobulins such as IgG, IgA, or IgM . Alternately, the M protein may belong to a light chain present in the urine or serum Impairment of the renal system as a consequence of multiple myeloma is one of the most common features Research has indicated that the impairment of renal function is often associated with survival rates of inferior order. The presence of hypercalcemia and light chain proteinuria are considered some of the primary causes of myeloma in a majority of the cases 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. Additionally, renal impairment occurs in most patients at a subsequent stage of multiple myeloma A large number of the patients develop severe renal impairment with the progression of the disease 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 Research has further indicated that there is evidence for the improvement of patients who have developed renal failure Certain studies in literature report that the reversal of renal impairment is often associated with improved rates of survival 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 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.

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 There is sufficient evidence that the free light chains have a vital role in the causation of the damage to renal functionality Most studies have indicated that in mouse and rat models, 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 The occurrence of damage to the renal function is considerably lower in animals which are treated with light chains obtained from patient samples However, there is no available evidence of renal disease There are considerable differences in the physicochemical properties present in the light chains 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 Consequently, a regular filtration of small amounts of various light chains occurs at the glomerulus . A reabsorption of these light chains in the proximal tubuli occurs along with a catabolization In cases of multiple myeloma, there is an increase in the ability of reabsorption and catabolization of the proximal tubular cells As a consequence, there is a lack of reabsorption of light chains in the proximal tubuli Therefore, the light chains reach the nephron at its distal segment 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 This obstruction in the distal tubuli typically leads to the leakage in the tubular content The tubular content leaks into the interstitium which results in the appearance of classic tubular cast and the kidney with myeloma 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 There are various factors that catalyze the formation of renal casts in most myeloma patients 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 Hypercalcaemia is likely to induce vasoconstriction which is followed by a reduction in the glomerular filtration rate Several medications, particularly non-steroidal anti-inflammatory drugs (NSAIDS) lead to the decrease in the blood flow in the renal system Agents of radiographic contrast lead to the induction of acute renal failure in patients of myeloma The renal failure is especially resulted in patients who have dehydration or the use of media of ionic contrast has been made.

Renal failure in multiple myeloma – management

Most patients with multiple myeloma typically experience a certain degree of insufficiency of renal function 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 Additionally, management of fluid rehydration, administration of glucocorticoids elements, or even discontinued administration of nephrotoxic drugs including NSAIDs . A considerable number of patients have the ability to recover in the initial period of six weeks Recovery at the later stages is possible in some patients as well wherein myeloma was found to be one of the most common diagnoses in patients who have been able to discontinue long term dialysis Plasma exchange and method of plasmapheresis have been primarily proposed as an effective method of prevention of renal failure associated with light chains . This is achieved by the removal of light chains from the plasma region 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 The efficacy of the treatment has been established in literature However, its efficacy has been found to be limited to patients with the syndrome of hyperviscosity A prospective study which is randomized and controlled is required for the decision of recommending the method of plasma exchange 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 The risk of failure of renal function increases along with the increase in the load of tumor However, the underlying tumor burden that ultimately leads to the determination of the rate of survival 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 The standard method of treatment of the treatment of the overt symptomatic disease is the method of chemotherapy for the melphalan and prednisone Research indicates that when chemotherapy is increased to five times the standard dosage, the rate of remission is also increased considerably The transplantation of the haematopoeitic stem cells have been found to lead to the reduction in the rate of death related to treatment 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 . Literature indicates that melphalan is the most suitable agent for chemotherapy of high dosage The patients with multiple myeloma induced renal failure showed great improvement in the rate of remission with the use of high dose chemotherapy . 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 However, in literature, there is an indication that high dosages of melphalan can lead to induction of renal failure Severe mucositis may also be resulted from high doses of melphalan and thus, it should be reduced Supportive therapies including biophosphonates are known as inhibitors of considerable potency for bone resorption In patients with multiple myeloma are used primarily for treatment of hypercalcaemia.

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Conclusion

For patients of multiple myeloma, the likelihood of incidence of renal impairment is high 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, administration of drugs of nephrotoxicity, infection, or agents of contrast, and proteinuria . 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 Since the rate of mortality of patients with multiple myeloma induced renal failure is considerably high, the early diagnosis and prevention is important 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 The crucial factors that affect the renal function include the degree of failure of renal function, incidence of hypercalcaemia, and excreted amounts of protein The effective treatment of failure of renal function along with myeloma therapy leads to the reduction of adverse events with prolonged rates of survival.

References

  • Kuo, VC, Fenves, AZ, and Mehta, AN (2011) “Multiple myeloma presenting as acute renal failure,” Proc Bayl Univ Med Cent, 24(4): 302–305.
  • Goldschmidt, H, Lannert, H, Bommer, J, and Ho, AD (2000) “Multiple myeloma and renal failure,” Nephrol Dial Transplant, 15: 301-304
  • Chu, P (2013) “Managing multiple myeloma patients with renal failure,” Hong Kong Journal of Nephrology, 15(2): 62-67
  • K.C. Abbott, L.Y. Agodoa (2001) “Multiple myeloma and light chain-associated nephropathy at end-stage renal disease in the United States: patient characteristics and survival,” Clin Nephrol, 56: 207–210
  • V. Eleutherakis-Papaiakovou, A. Bamias, D. Gika, A. Simeonidis, A. Pouli, A. Anagnostopoulos, et al. (2007) Renal failure in multiple myeloma: incidence, correlations, and prognostic significance Leuk Lymphoma, 48: 337–341
 
 
 
 
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