Clinical and morphological options of kidney damage in case of myeloma disease

There are clinical and morphological options of kidney disease in case of myeloma disease (multiple myeloma, Rustickyi-Kaler’s disease, generalized plasmacytoma) in literature survey. Myeloma takes 10–15% in the structure of oncohematological diseases. Kidney damage can be the only or the first demonstration of the myeloma nephropathy. Kidney damage connected with myeloma includes myeloma tubular nephropathy (50%), AL-amyloidosis (10–20%), L-chain disease (5–10%) and some other states.

COMPARATIVE CHARACTERISTICS OF RENAL BLOOD FLOW IN PATIENTS WITH CHRONIC RENAL FAILURE DEVELOPED AS A RESULT OF MYELOMA NEPHROPATHY AND IN PRIMARY NEPHROLOGY PATHOLOGY

A comparative analysis of the indicators of renal hemodynamics in patients with chronic renal failure/chronic kidney disease (CRF/CKD) developed against myeloma nephropathy (group 1) and with primary kidney disease (group 2) was done. 20 patients were included in the first group, 14 patients were in the second one, and in most cases there was Stage 3 CRF/CKD. There were analyzed the following indicators of renal blood flow: peak systolic velocity, end diastolic velocity, mean flow velocity throughout the entire cardiac cycle, resistive index and pulsation index. Circulation figures were recorded at the level of basic, segmental, interlobar, arc, interlobular renal arteries. It is concluded that violations of renal blood flow and vascular resistance in patients with multiple myeloma complicated by chronic renal failure are primarily due to CKD itself. The differences in the two groups of patients with CRF/CKD were only about the average level in the parenchymal blood flow velocity (interlobular, arcuate, interlobar arteries); at myeloma nephropathy it was significantly reduced in comparison with the control group and patients with CRF/CKD without hemoblastosis. The rest velocity parameters were significantly reduced and vascular resistance indices were increased in comparison with the control and did not differ in groups of patients with CRF/CKD. Thus, hemodynamic changes at the level of parenchyma are the most important for patients with multiple myeloma, which suggests more severe violations of kidneys in these patients with the complication of CRF.

EARLY APPLICATION OF HIGH CUT-OFF HAEMODYALISIS FOR DE-NOVO MYELOMA NEPHROPATHY IS ASSOCIATED WITH LONG-TERM DIALYSIS-INDEPENDENCY AND RENAL RECOVERY

BackgroundMultiple myeloma (MM) is a haematological malignancy associated with kidney injury resulting from cast nephropathy, which can be caused by monoclonal free light chains (FLC). It has been demonstrated that reduction of FLC can lead to a higher proportion of patients recovering renal function with a better outcome, especially if extended high cut-off haemodialysis (HCO-HD) combined with chemotherapy is used.Patients and MethodsIn this study, four cases of MM nephropathy were treated with HCO-HD and chemotherapy at a single institution during the period from August 2009 to August 2011. All of the patients presented with acute renal failure and high serum FLC. All patients underwent a bone marrow biopsy to confirm the diagnosis of MM, according to the WHO criteria. Three patients had de-novo MM and one patient had relapsed light chain myeloma disease. All patients underwent HCO-HD concomitantly with specific myeloma therapy once the diagnosis or relapse of MM was established.ResultsAfter a median follow up of 26 months, (range, 13-36) our data showed that all patients had a significant decrease in serum FLC through HCO-HD, proving the effectiveness of HCO-HD in managing MM. De-novo MM patients restored their renal function and achieved low-level FLC early on the treatment and become dialysis-independent. One patient with relapsed myeloma remained dialysis dependant.ConclusionOur study suggests that if myeloma nephropathy associated with light-chain disease, HCO-HD should be initiated as early as possible. At the same time a specific MM treatment should be initiated to gain control of the disease and salvage the kidneys in order to achieve dialysis-independency. Further trials to confirm our results are warranted.Key Words: Multiple myeloma, renal failure, High cut-off haemodialysis, chemotherapy, outcome.

Mutational Analysis in Murine Models for Myeloma-Associated Fanconi’s Syndrome or Cast Myeloma Nephropathy

We have designed an in vivo model in which murine hybridoma cell clones producing human Ig light chains (LC) are administred to mice. Depending on which monoclonal LC is expressed, this model mimicks either cast myeloma nephropathy or the pathological condition defined as myeloma-associated Fanconi’s syndrome (FS) with LC crystallization. Morphological alterations of the kidney cells are thus obtained in mice. All studied LC are closely related human monoclonal VκI proteins, which differ by a limited number of substitutions within the variable region. In the case of an FS monoclonal LC, we show that limited changes introduced through site-directed mutagenesis in the variable domain may suppress formation of intracellular crystals within tubular cells. We also show that multiple peculiarities of the variable region are simultaneously needed to allow LC crystallization; this property thus likely results from a unique LC tridimensional conformation imposed by concomitant somatic mutations of a specific germinally encoded framework.