TREATMENT

Initial treatment:
Thalidomide or lenalidomide + dexamethasone Bortezomib + dexamethasone Bortezomib + lenalidomide + dexamethasone Melphalane + prednisone + lenalidomide/thalidomide

Bisphosphonates as adjunctive Rx

Types of renal disease in multiple myeloma

Renal disease is a common problem in multiple myeloma. The pathology is heterogeneous and may involve a variety of different mechanisms TYPES OF RENAL DISEASE The types of kidney disease that occur among patients with multiple myeloma can be classified by the primary site of injury:

 Glomerular Primary amyloidosis Monoclonal immunoglobulin deposition disease Miscellaneous

Tubular Light chain cast nephropathy Distal tubular dysfunction Proximal tubulopathy or acquired Fanconi's syndrome

 Interstitial Plasma cell infiltration Interstitial nephritis

 In addition, patients with multiple myeloma are vulnerable to the toxic effects of medications and contrast exposure. Such patients may develop acute tubular necrosis (ATN) related to drugs or contrast, or collapsing focal and segmental glomerulosclerosis related to bisphosphonates

MYELOMA CAST NEPHROPATHY

over-production, filtration and overabundance of toxic light chains in the ascending loop of Henle. Tamm-Horsfall mucoprotein leading to both tubular injury and intratubular cast formation and obstruction Volume depletion is a significant risk factor elevated creatinine and minimal proteinuria on 24 hour urine electrophoresis studies, in cast nephropathy most of the proteinuria will be secondary to monoclonal light chains,

AMYLOIDOSIS
In amyloidosis, the circulating light chains are taken up by and partially metabolized in macrophages. Light chain fragments are then secreted from the macrophages, and these fragments can precipitate to form the characteristic Congo red positive, -pleated fibrils

Patients commonly present with nephrotic range proteinuria. The urine dipstick for protein is positive among patients with amyloidosis, given that albuminuria is present due to the glomerular leak On 24 hour urine electrophoresis studies, most of the proteinuria will consist of albumin, and the monoclonal light chain component will be small The serum creatinine may be normal or only mildly elevated.

MONOCLONAL IMMUNOGLOBULIN DEPOSITION DISEASE (MIDD)

Monoclonal immunoglobulin deposition disease (MIDD) is pathogenetically similar to amyloidosis, except that the light (or heavy) chain fragments do not form fibrils and the deposits are Congo red negative . The urine dipstick for protein is positive among patients with MIDD. On 24 hour urine electrophoresis studies, as in amyloidosis, most of the proteinuria will consist of albumin, and the monoclonal light chain component will be small

RENAL TUBULAR DYSFUNCTION

In some patients, light chains cause only tubular dysfunction, with the glomerular filtration rate being relatively well maintained. The proximal tubules are most prominently affected, due to the reabsorption of filtered light chains and their subsequent accumulation in the proximal tubular cells. Nearly 90 percent of the light chains involved are kappa . The clinical manifestations of tubular dysfunction include signs of the Fanconi syndrome such as proximal renal tubular acidosis and phosphate wasting; An important laboratory finding is the presence of hypouricemia normoglycemic glycosuria as well as aminoaciduria

OTHER CAUSES OF ACUTE KIDNEY INJURY (AKI)

Hypercalcemia
Hypercalcemia is a common finding in multiple myeloma, with 15 percent of patients having a calcium concentration >11.0 mg/dL at the time of diagnosis. Hypercalcemia can contribute to the development of renal failure by causing renal vasoconstriction, by leading to intratubular calcium deposition, and perhaps by increasing the toxicity of filtered light chains . The decline in renal function may be associated with patient complaints of polyuria and polydipsia due to nephrogenic diabetes insipidus. Both the renal failure and ADH resistance induced by hypercalcemia are generally reversible

Bisphosphonates
Bisphosphonates are commonly used among patients with multiple myeloma and lytic bone lesions.

Bisphosphonates have been associated with ATN (zoledronate) and the collapsing form of focal and segmental glomerulosclerosis (pamidronate).