Nephrology for General Practitioners - O.I. Bakaliuk 2003

Renal Pathology in Systemic and Other Diseases
Renal Involvement in Multiple Myeloma

Renal pathology in multiple myeloma is often a leading manifestation of the disease, posing significant diagnostic challenges, especially in the absence of other clinical, laboratory, and instrumental criteria—such as bone pain, osteolytic lesions and fractures, weight loss, hyperproteinemia, elevated ESR, Bone Marrow plasma Cell infiltration, the presence of an M-spike in Blood Plasma and urine, and Bence Jones Proteins in the urine.

The term «myeloma nephropathy» encompasses a group of distinct renal lesions, including primary myeloma nephropathy with its characteristic morphological picture, secondary amyloidosis, nephrocalcinosis, and renal failure (N. E. Andreeva, 1987).

The primary mechanism of renal injury in multiple myeloma is overflow proteinuria, which is associated with the passage of large amounts of abnormal protein through the renal structures and its accumulation in the basement membrane of capillaries and the interstitium in the form of casts. These casts are composed of immunoglobulin light chains (kappa, lambda), other Plasma Proteins (albumin), and Tamm-Horsfall protein. Their formation is linked to the appearance of altered immunoglobulin light chains that are freely filtered in the glomeruli and only partially reabsorbed by the tubules. The tubulotoxic effect of these chains is accompanied by necrosis of proximal tubular Cells. In the distal tubules and collecting ducts, precipitation of Bence Jones and Tamm-Horsfall proteins occurs, leading to cast formation. These casts become surrounded by monocytes migrating from the interstitium, resulting in multinucleated giant structures that completely obstruct the tubular lumen.

Pathognomonic for multiple myeloma is the involvement of the tubules themselves, with lumen obstruction and The formation of «tunnels» into the interstitial space. Metabolic disturbances—specifically hypercalcemia and hyperuricemia leading to nephrocalcinosis—also play a role in renal impairment.

A distinctive feature of the urinary syndrome in myeloma nephropathy is relatively isolated proteinuria, although aseptic leukocyturia and significant cylindruria (granular casts) are occasionally detected. It should be emphasized that massive proteinuria in multiple myeloma is never accompanied by hypoproteinemia, unlike Nephrotic Syndrome. Manifestations of tubular dysfunction include glucosuria, Aminoaciduria, exceptionally high phosphaturia and uricosuria, and proximal Renal Tubular Acidosis.

Myeloma nephropathy may manifest as the onset and rapid progression of acute or chronic renal failure. Causes of ACUTE RENAL FAILURE include dehydration, hypercalcemia, and The Use of radiocontrast agents for diagnostic purposes.

L. D. Sidorova et al. (1988), based on morphological studies, distinguish three stages in The Development of myeloma nephropathy.

Stage I (preclinical) is characterized by mild Protein dystrophy of the nephrothelium; interstitial changes are absent. Urinalysis findings are virtually normal.

In Stage II, prominent granular, hyaline-droplet, and hydropic degeneration, tubular epithelial atrophy, numerous eosinophilic casts in the tubular lumen, foci of interstitial sclerosis, and thickening of the glomerular capillary basement membrane are observed. These changes resemble the early phase of diabetic glomerulosclerosis. Characteristic features include varying degrees of proteinuria, Hematuria, leukocyturia, calciuria, uricosuria, hyposthenuria, and a decrease in creatinine clearance.

Morphological changes in Stage III are specific and highly characteristic: blockade of the majority of tubules by eosinophilic and granular casts, tubular epithelial atrophy, interstitial sclerosis, thickening of the glomerular capillary basement membrane, mesangial expansion, and nephrocalcinosis. The clinical picture is marked by the progression of renal failure symptoms—nocturia, hypo- and isosthenuria, hypercreatininemia, hyperazotemia, decreased urea and creatinine clearance, and the onset of Renal Arterial Hypertension. Overall, myeloma nephropathy typically follows a progressive course, invariably leading to end-stage renal failure.

Diagnosis of Other forms of renal involvement, with the exception of secondary amyloidosis (which is verified by percutaneous renal biopsy), is carried out using conventional Methods (ultrasound, duplex Doppler sonography, radioisotope renography, urine culture for sterility); meanwhile, the use of radiocontrast agents must be strictly avoided.

Standard therapy for multiple myeloma includes the administration of Hormones and cytotoxic agents, and interferon during the remission period.