The pathological features of leukemic cells infiltrating the renal interstitium in chronic lymphocytic leukemia/small lymphocytic lymphoma from a large single Chinese center

Background Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is rare in Asians, and patients with CLL/SLL seldomly undergo kidney biopsy. The histopathological features and clinical relevance of tubulointerstitial injury in CLL/SLL have not been extensively characterized. Hence, we attempted to describe the clinical characteristics, renal pathology and clinical outcome of a well-characterized population of CLL/SLL patients with CLL cell infiltration in the renal interstitium from a large single center in China. Methods Between January 1st, 2010 and September 31st, 2020, 31946renal biopsies were performed at Peking University First Hospital, and 10 CLL/SLL patients with CLL cell infiltration in the renal interstitium were included. Complete clinical data were collected from these 10 patients, and renal specimens were examined by routine light microscopy, immunofluorescence and electron microscopy. Results The extent of the infiltrating CLL cells in patients with CLL/SLL varied among different patients and ranged from 10 to 90% of kidney parenchyma. Six (60%) of 10 patients presented with an extent of infiltrating CLL cells ≥50%. Interestingly, we found that three patients (3/10, 30%) expressed monoclonal immunoglobulins in the infiltrating CLL cells, and special cytoplasmic crystalline structures were found in two of the three patients by electron microscopy for the first time. Severe renal insufficiency (Scr ≥200 μmol/L) was associated with ≥50% interstitial infiltration of CLL cells in the renal interstitium. Conclusions The current study confirmed that CLL cells infiltrating the renal interstitium can directly secrete monoclonal immunoglobulins, indicating that the interstitial infiltrating CLL cells possibly cause renal injury directly by secreting monoclonal immunoglobulins in situ. This finding may prove a new clue to elucidate the pathogenetic mechanism of renal injury involved with CLL/SLL.

The Clone Wars: Diagnosing and Treating Dysproteinemic Kidney Disease in the Modern Era

Dysproteinemic kidney diseases are disorders that occur as the result of lymphoproliferative (B cell or plasma cell) disorders that cause kidney damage via production of nephrotoxic monoclonal immunoglobulins or their components. These monoclonal immunoglobulins have individual physiochemical characteristics that confer specific nephrotoxic properties. There has been increased recognition and revised characterization of these disorders in the last decade, and in some cases, there have been substantial advances in disease understanding and treatments, which has translated to improved patient outcomes. These disorders still present challenges to nephrologists and patients, since they are rare, and the field of hematology is rapidly changing with the introduction of novel testing and treatment strategies. In this review, we will discuss the clinical presentation, kidney biopsy features, hematologic characteristics and treatment of dysproteinemic kidney diseases.

The pathological features of leukemic cells infiltrating the renal interstitium in chronic lymphocytic leukemia/small lymphocytic lymphoma from a large single Chinese center

Background Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is rare in Asians, and patients with CLL/SLL seldomly undergo kidney biopsy. The histopathological features and clinical relevance of tubulointerstitial injury in CLL/SLL have not been extensively charaterized. Hence, we attempted to describe the clinical characteristics, renal pathology and clinical outcome of a well-characterized population of CLL/SLL patients with CLL cell infiltration in the renal interstitium from a large single center in China. Methods Between January 1st, 2010 and September 31st, 2020, 31946 renal biopsy pathologies were performed at Peking University First Hospital, and 10 CLL/SLL patients with CLL cell infiltration in the renal interstitium were included. Complete clinical data were collected from these 10 patients, and renal specimens were examined by routine light microscopy, immunofluorescence and electron microscopy. Results The extent of the infiltrating CLL cells in patients with CLL/SLL varied among different patients and ranged from 10–90% of kidney parenchyma. Six (60%) of 10 patients presented with an extent of infiltrating CLL cells ≥ 50%. Interestingly, we found that three patients (3/10, 30%) expressed monoclonal immunoglobulins in the infiltrating CLL cells, and special cytoplasmic crystalline structures were found in two of the three patients by electron micriscopy for the first time. Severe renal insufficiency (Scr ≥ 200 µmol/L ) was associated with ≥ 50% interstitial infiltration of CLL cells in the renal interstitium. Conclusions The findings confirmed that CLL cells infiltrating the renal interstitium can directly secrete monoclonal immunoglobulins, indicating that the interstitial infiltrating CLL cells probably cause renal injuriy directly by secreting monoclonal immunoglobulins in situ. This finding may prove a new clue to elucidate the pathogenetic mechanism of renal injury involved with CLL/SLL .

Randall-Type Monoclonal Immunoglobulin Deposition Disease: New Insights into the Pathogenesis, Diagnosis and Management

Randall-type monoclonal immunoglobulin deposition disease (MIDD) is a rare disease that belongs to the spectrum of monoclonal gammopathy of renal significance (MGRS). Renal involvement is prominent in MIDD, but extra-renal manifestations can be present and may affect global prognosis. Recent data highlighted the central role of molecular characteristics of nephrotoxic monoclonal immunoglobulins in the pathophysiology of MIDD, and the importance of serum free light chain monitoring in the diagnosis and follow-up disease. Clone-targeted therapy is required to improve the overall and renal survival, and the achievement of a rapid and deep hematological response is the goal of therapy. This review will focus on the recent progress in the pathogenesis and management of this rare disease.

Comparison of Monoclonal Gammopathies Linked to Poliovirus or Coxsackievirus vs. Other Infectious Pathogens

Chronic stimulation by infectious pathogens or self-antigen glucosylsphingosine (GlcSph) can lead to monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Novel assays such as the multiplex infectious antigen microarray (MIAA) and GlcSph assays, permit identification of targets for >60% purified monoclonal immunoglobulins (Igs). Searching for additional targets, we selected 28 purified monoclonal Igs whose antigen was not represented on the MIAA and GlcSph assays; their specificity of recognition was then analyzed using microarrays consisting of 3760 B-cell epitopes from 196 pathogens. The peptide sequences PALTAVETG and PALTAAETG of the VP1 coat proteins of human poliovirus 1/3 and coxsackievirus B1/B3, respectively, were specifically recognized by 6/28 monoclonal Igs. Re-analysis of patient cohorts showed that purified monoclonal Igs from 10/155 MGUS/SM (6.5%) and 3/147 MM (2.0%) bound to the PALTAVETG or PALTAAETG epitopes. Altogether, PALTAV/AETG-initiated MGUS are not rare and few seem to evolve toward myeloma.

The Pathological Features of Leukaemic Cells Infiltrating Renal Interstitium in Chronic Lymphocytic Leukaemia/small Lymphocytic Lymphoma Within 10 Years in a Large Single Chinese Centre

Background Chronic lymphocytic leukemia/Small Lymphocytic Lymphoma (CLL/SLL) was rare in Asians and patients with CLL/SLL rarely undergo kidney biopsy. Little information is available on the histopathological features and clinical relevance of CLL/SLL tubulointerstitial injury. Hence, we attempted to describe the clinical characteristics, renal pathology and clinical outcome of a well characterized population of CLL/SLL patients with CLL infiltration in renal interstitium from a large single center in China.Methods Between January 1st, 2010 to September 31st, 2020, 31946 reanl biopsy pathology were performed at Peking University First Hospital and 10 patients with CLL infiltration in renal interstitium were included. Complete clinical data were collected from these 10 patients and the renal specimens were examined by routine light microscopy, immunonuorescence and electron microscopy examination.Results The extent of infiltrating CLL cells was diverse between different patients, from 10% to 90%. Five patients presented interstitial infiltration with the percent of infiltrate CLL cells≥50%. Proliferation centers were formed in the renal interstitium of 6 patients (6/10, 60%). Intrestingly, we found three patients (3/10, 30%) expressed monoclonal immunoglobulin in infiltrating CLL cells and special crystal structures were found in these cells in two of the three patients for the first time. Conclusions The finding confirmed CLL cells infiltrating in renal interstitium can secret monoclonal immunoglobulins directly, indicating that CLL cells in renal interstitium probably directly involved in local lesion injurys by secrecting monoclonal immunoglobulin. This finding will help understanding the mechanism of renal injury with CLL infiltration, thereby improving our current therapeutic efforts.

The Pathological Features of Leukaemic Cells Infiltrating Renal Interstitium in Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma Within 10 Years in a Large Single Chinese Centre

Background Chronic lymphocytic leukemia/Small Lymphocytic Lymphoma (CLL/SLL) was rare in Asians and patients with CLL/SLL rarely undergo kidney biopsy. Little information is available on the histopathological features and clinical relevance of CLL/SLL tubulointerstitial injury. Hence, we attempted to describe the clinical characteristics, renal pathology and clinical outcome of a well characterized population of CLL/SLL patients with CLL infiltration in renal interstitium from a large single center in China.Methods Between January 1st, 2010 to September 31st, 2020, 31946 reanl biopsy pathology were performed at Peking University First Hospital and 10 patients with CLL infiltration in renal interstitium were included. Complete clinical data were collected from these 10 patients and the renal specimens were examined by routine light microscopy, immunonuorescence and electron microscopy examination.Results The extent of infiltrating CLL cells was diverse between different patients, from 10% to 90%. Five patients presented interstitial infiltration with the percent of infiltrate CLL cells≥50%. Proliferation centers were formed in the renal interstitium of 6 patients (6/10, 60%). Intrestingly, we found three patients (3/10, 30%) expressed monoclonal immunoglobulin in infiltrating CLL cells and special crystal structures were found in these cells in two of the three patients for the first time. Conclusions The finding confirmed CLL cells infiltrating in renal interstitium can secret monoclonal immunoglobulins directly, indicating that CLL cells in renal interstitium probably directly involved in local lesion injurys by secrecting monoclonal immunoglobulin. This finding will help understanding the mechanism of renal injury with CLL infiltration, thereby improving our current therapeutic efforts.