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  1. Article ; Online: Management of Patients with Kidney Failure and Pericarditis.

    Rosen, Raphael J / Valeri, Anthony M

    Clinical journal of the American Society of Nephrology : CJASN

    2022  Volume 18, Issue 2, Page(s) 270–272

    MeSH term(s) Humans ; Pericarditis/drug therapy ; Kidney Failure, Chronic
    Language English
    Publishing date 2022-11-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2226665-3
    ISSN 1555-905X ; 1555-9041
    ISSN (online) 1555-905X
    ISSN 1555-9041
    DOI 10.2215/CJN.07470622
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  2. Article ; Online: Clinicopathologic Characteristics, Etiologies, and Outcome of Secondary Oxalate Nephropathy.

    Nasr, Samih H / Valeri, Anthony M / Said, Samar M / Sethi, Sanjeev / Nath, Karl A / Lieske, John C / Bu, Lihong

    Mayo Clinic proceedings

    2024  Volume 99, Issue 4, Page(s) 593–606

    Abstract: Objective: To report the clinicopathologic characteristics, prognostic indicators, prognosis, and transplant outcome of secondary oxalate nephropathy (ON).: Patients and methods: We performed a retrospective analysis of 113 consecutive patients with ... ...

    Abstract Objective: To report the clinicopathologic characteristics, prognostic indicators, prognosis, and transplant outcome of secondary oxalate nephropathy (ON).
    Patients and methods: We performed a retrospective analysis of 113 consecutive patients with secondary ON diagnosed at Mayo Clinic in Rochester, Minnesota, between January 1, 2001, and March 1, 2023.
    Results: The incidence of secondary ON among all native biopsies from Mayo Clinic patients over the study period (n=11,617) was 0.97%. ON was attributed to enteric hyperoxaluria in 60% of the 113 patients (68; most commonly Roux-en-Y gastric bypass), excessive ingestion of foods high in oxalate or oxalate precursors in 23% (26) (most commonly vitamin C), and idiopathic in 17% (19). Most patients presented with acute kidney injury (AKI) (particularly in the ingestion group) or AKI on chronic kidney disease, and 53% (60 of 113) were diabetic. Calcium oxalate crystals were accompanied by acute tubular injury, inflammation, and interstitial fibrosis and tubular atrophy. Concurrent pathologic conditions were present in 53% of the patients (60 of 113), most commonly diabetic nephropathy. After a median follow-up of 36 months, 27% of the patients (30 of 112) had kidney recovery, 19% (21 of 112) had persistent kidney dysfunction, 54% (61 of 112) had development of kidney failure, and 29% (32 of 112) died. The mean kidney survival was worse for patients with a concurrent pathologic lesion (30 months vs 96 months for those without a concurrent pathologic lesion; P<.001). Independent predictors of kidney failure were the degree of interstitial fibrosis and tubular atrophy and nadir estimated glomerular filtration rate but not the degree of crystal deposition. After a median follow-up of 58 months in 23 patients who received kidney transplant, 4 had graft loss (due to ON in 3). The 2-, 5-, and 10-year graft survivals were 90% (18 of 20), 79% (11 of 14), and 50% (6 of 12).
    Conclusion: ON is a rare cause of AKI or AKI on chronic kidney disease. Most patients have comorbid pathologic conditions, particularly diabetic nephropathy, which worsen the prognosis. Recurrence in the renal allograft and graft loss may occur if hyperoxaluria is not controlled.
    MeSH term(s) Humans ; Kidney Transplantation/adverse effects ; Diabetic Nephropathies/complications ; Retrospective Studies ; Hyperoxaluria/complications ; Hyperoxaluria/epidemiology ; Acute Kidney Injury/etiology ; Acute Kidney Injury/complications ; Oxalates ; Renal Insufficiency, Chronic/complications ; Fibrosis ; Atrophy/complications
    Chemical Substances Oxalates
    Language English
    Publishing date 2024-02-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 124027-4
    ISSN 1942-5546 ; 0025-6196
    ISSN (online) 1942-5546
    ISSN 0025-6196
    DOI 10.1016/j.mayocp.2023.08.014
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  3. Article ; Online: The prevalence and clinical outcomes of microangiopathic hemolytic anemia in patients with biopsy-proven renal thrombotic microangiopathy.

    Bhutani, Gauri / Leung, Nelson / Said, Samar M / Valeri, Anthony M / Astor, Brad C / Fidler, Mary E / Alexander, Mariam P / Cornell, Lynn D / Nasr, Samih H

    American journal of hematology

    2022  Volume 97, Issue 11, Page(s) E426–E429

    MeSH term(s) Anemia, Hemolytic/etiology ; Biopsy ; Humans ; Prevalence ; Purpura, Thrombotic Thrombocytopenic ; Thrombotic Microangiopathies/epidemiology ; Thrombotic Microangiopathies/etiology
    Language English
    Publishing date 2022-09-10
    Publishing country United States
    Document type Letter
    ZDB-ID 196767-8
    ISSN 1096-8652 ; 0361-8609
    ISSN (online) 1096-8652
    ISSN 0361-8609
    DOI 10.1002/ajh.26705
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  4. Article ; Online: The characteristics of seronegative and seropositive non-hepatitis-associated cryoglobulinemic glomerulonephritis.

    Javaugue, Vincent / Valeri, Anthony M / Jaffer Sathick, Insara / Said, Samar M / Erdogan Damgard, Sibel / Murray, David L / Klobucher, Tyler / Andeen, Nicole K / Sethi, Sanjeev / Fervenza, Fernando C / Leung, Nelson / Nasr, Samih H

    Kidney international

    2022  Volume 102, Issue 2, Page(s) 382–394

    Abstract: The clinicopathologic characteristics and long-term outcome of non-hepatitis-associated cryoglobulinemic glomerulonephritis (CryoGN) are not well-defined and cases with undetectable serum cryoglobulin (seronegative CryoGN) have not been investigated. To ... ...

    Abstract The clinicopathologic characteristics and long-term outcome of non-hepatitis-associated cryoglobulinemic glomerulonephritis (CryoGN) are not well-defined and cases with undetectable serum cryoglobulin (seronegative CryoGN) have not been investigated. To resolve this, we retrospectively identified 81 patients with biopsy-proven non-hepatitis CryoGN, including 22 with seronegative CryoGN. The median age was 61 years and 76% presented with nephritic syndrome. A hematologic condition was found in 89% of patients, including monoclonal gammopathy of renal significance (65%) and symptomatic lymphoproliferative disorder (35%). In the seropositive group, 56% had type II, 29% type I, and 8% type III cryoglobulin. Extrarenal manifestations, mostly of skin, were present in 64% and were significantly less common in seronegative CryoGN. Glomerular deposits by immunofluorescence were IgM dominant (84%) and polytypic (70%) in the seropositive group, whereas 52% of seronegative cases had monotypic deposits (i.e., type I cryoglobulin). Ultrastructurally, the deposits were organized in 77% of cases. Substructure appearance significantly differed according to the type of CryoGN, forming most commonly short cylindrical structures in type II and other organized substructures in type I CryoGN. Most patients were treated with clone-directed therapy. On follow up (median 33 months), 77% had partial or complete remission, 10% reached kidney failure and 14% died. Predictors of kidney failure on univariate analysis were AKIN stage 3, positive rheumatoid factor and biclonal gammopathy at diagnosis. We conclude that most CryoGN cases (types I and II) are due to a hematologic condition and are associated with favorable outcome after clone-directed therapy. Seronegative CryoGN accounts for about a quarter of cases and is mostly a kidney-limited disease. Thus, further investigations are needed to unravel the pathophysiology of seronegative CryoGN.
    MeSH term(s) Cryoglobulins ; Glomerulonephritis/diagnosis ; Glomerulonephritis/etiology ; Glomerulonephritis/pathology ; Humans ; Middle Aged ; Paraproteinemias/pathology ; Renal Insufficiency ; Retrospective Studies
    Chemical Substances Cryoglobulins
    Language English
    Publishing date 2022-05-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2022.03.030
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  5. Article: Characteristics of patients with coexisting DNAJB9-associated fibrillary glomerulonephritis and IgA nephropathy.

    Said, Samar M / Rocha, Alejandro Best / Valeri, Anthony M / Sandid, Mohamad / Ray, Anhisekh Sinha / Fidler, Mary E / Alexander, Mariam Priya / Larsen, Christopher P / Nasr, Samih H

    Clinical kidney journal

    2020  Volume 14, Issue 6, Page(s) 1681–1690

    Abstract: Background: Coexistence of fibrillary glomerulonephritis (FGN) and immunoglobulin A (IgA) nephropathy (IgAN) in the same kidney biopsy (FGN-IgAN) is rare, and the clinicopathologic characteristics and outcome of this dual glomerulopathy are unknown.: ... ...

    Abstract Background: Coexistence of fibrillary glomerulonephritis (FGN) and immunoglobulin A (IgA) nephropathy (IgAN) in the same kidney biopsy (FGN-IgAN) is rare, and the clinicopathologic characteristics and outcome of this dual glomerulopathy are unknown.
    Methods: In this study, 20 patients with FGN-IgAN were studied and their characteristics were compared with 40 FGN and 40 IgAN control patients.
    Results: Concurrent IgAN was present in 1.8% of 847 consecutive FGN cases and was the second most common concurrent glomerulopathy after diabetic nephropathy. FGN-IgAN patients were overwhelmingly White (94%) and contrary to FGN patients were predominantly (60%) males. Compared with IgAN patients, FGN-IgAN patients were older, had higher proteinuria, a higher incidence of renal insufficiency, and a lower incidence of microhematuria and gross hematuria at diagnosis. Six (30%) patients had malignancy, autoimmune disease or hepatitis C infection, but none had a secondary cause of IgAN or clinical features of Henoch-Schonlein purpura. Histologically, all cases exhibited smudgy glomerular staining for immunoglobulin G and DnaJ homolog subfamily B member 9 (DNAJB9) with corresponding fibrillary deposits and granular mesangial staining for IgA with corresponding mesangial granular electron-dense deposits. On follow-up (median 27 months), 10 of 18 (56%) FGN-IgAN patients progressed to end-stage kidney disease (ESKD), including 5 who subsequently died. Serum creatinine at diagnosis was a poor predictor of renal survival. The proportion of patients reaching ESKD or died was higher in FGN-IgAN than in IgAN. The median Kaplan-Meier ESKD-free survival time was 44 months for FGN-IgAN, which was shorter than IgAN (unable to compute, P =
    Conclusions: FGN-IgAN is very rare, with clinical presentation and demographics closer to FGN than IgAN. Prognosis is guarded with a median renal survival of 3.6 years. The diagnosis of this dual glomerulopathy requires careful evaluation of immunofluorescence findings, and electron microscopy or DNAJB9 immunohistochemistry.
    Language English
    Publishing date 2020-12-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 2655800-2
    ISSN 2048-8513 ; 2048-8505
    ISSN (online) 2048-8513
    ISSN 2048-8505
    DOI 10.1093/ckj/sfaa205
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  6. Article ; Online: Translating gene drive science to promote linguistic diversity in community and stakeholder engagement.

    Cheung, Cynthia / Gamez, Stephanie / Carballar-Lejarazú, Rebeca / Ferman, Victor / Vásquez, Váleri N / Terradas, Gerard / Ishikawa, Judy / Schairer, Cynthia E / Bier, Ethan / Marshall, John M / James, Anthony A / Akbari, Omar S / Bloss, Cinnamon S

    Global public health

    2020  Volume 15, Issue 10, Page(s) 1551–1565

    Abstract: Information about genetic engineering (GE) for vector control in the United States is disseminated primarily in English, though non-English speakers are equally, and in some geographic regions even more affected by such technologies. Non-English-speaking ...

    Abstract Information about genetic engineering (GE) for vector control in the United States is disseminated primarily in English, though non-English speakers are equally, and in some geographic regions even more affected by such technologies. Non-English-speaking publics should have equal access to such information, which is especially critical when the technology in question may impact whole communities. We convened an interdisciplinary workgroup to translate previously developed narrated slideshows on gene drive mosquitoes from English into Spanish, reviewing each iteration for scientific accuracy and accessibility to laypeople. Using the finalised stimuli, we conducted five online, chat-based focus groups with Spanish-speaking adults from California. Overall, participants expressed interest in the topic and were able to summarise the information presented in their own words. Importantly, participants asked for clarification and expressed scepticism about the information presented, indicating critical engagement with the material. Through collaboration with Spanish-speaking scientists engaged in the development of GE methods of vector control, we translated highly technical scientific information into Spanish that successfully engaged Spanish-speaking participants in conversations about this topic. In this manuscript, we document the feasibility of consulting Spanish-speaking publics about a complex emerging technology by drawing on the linguistic diversity of the scientific teams developing the technology.
    MeSH term(s) Adult ; Animals ; Community Participation ; Gene Drive Technology ; Hispanic Americans/psychology ; Hispanic Americans/statistics & numerical data ; Humans ; Linguistics ; Mosquito Control/methods ; Mosquito Vectors/genetics ; Stakeholder Participation ; Translating ; United States
    Language English
    Publishing date 2020-06-26
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2234129-8
    ISSN 1744-1706 ; 1744-1692
    ISSN (online) 1744-1706
    ISSN 1744-1692
    DOI 10.1080/17441692.2020.1779328
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  7. Article ; Online: Presentation and Outcomes of Patients with ESKD and COVID-19.

    Valeri, Anthony M / Robbins-Juarez, Shelief Y / Stevens, Jacob S / Ahn, Wooin / Rao, Maya K / Radhakrishnan, Jai / Gharavi, Ali G / Mohan, Sumit / Husain, S Ali

    Journal of the American Society of Nephrology : JASN

    2020  Volume 31, Issue 7, Page(s) 1409–1415

    Abstract: Background: The relative immunosuppression and high prevalence of comorbidities in patients with ESKD on dialysis raise concerns that they may have an elevated risk of severe coronavirus disease 2019 (COVID-19), but outcomes for COVID-19 in such ... ...

    Abstract Background: The relative immunosuppression and high prevalence of comorbidities in patients with ESKD on dialysis raise concerns that they may have an elevated risk of severe coronavirus disease 2019 (COVID-19), but outcomes for COVID-19 in such patients are unclear.
    Methods: To examine presentation and outcomes of COVID-19 in patients with ESKD on dialysis, we retrospectively collected clinical data on 59 patients on dialysis who were hospitalized with COVID-19. We used Wilcoxon rank sum and Fischer exact tests to compare patients who died versus those still living.
    Results: Two of the study's 59 patients were on peritoneal dialysis, and 57 were on hemodialysis. Median age was 63 years, with high prevalence of hypertension (98%) and diabetes (69%). Patients who died were significantly older than those still living (median age, 75 versus 62 years) and had a higher median Charlson comorbidity index (8 versus 7). The most common presenting symptoms were fever (49%) and cough (39%); initial radiographs most commonly showed multifocal or bilateral opacities (59%). By end of follow-up, 18 patients (31%) died a median 6 days after hospitalization, including 75% of patients who required mechanical ventilation. Eleven of those who died had advanced directives against intubation. The remaining 41 patients (69%) were discharged home a median 8 days after admission. The median initial white blood cell count was significantly higher in patients who died compared with those still living (7.5 versus 5.7×10
    Conclusions: The association of COVID-19 with high mortality in patients with ESKD on dialysis reinforces the need to take appropriate infection control measures to prevent COVID-19 spread in this vulnerable population.
    MeSH term(s) Adult ; Age Factors ; Aged ; COVID-19 ; Cause of Death ; Cohort Studies ; Comorbidity ; Coronavirus Infections/diagnosis ; Coronavirus Infections/epidemiology ; Coronavirus Infections/therapy ; Female ; Hospital Mortality/trends ; Hospitalization/statistics & numerical data ; Hospitals, University ; Humans ; Infection Control/organization & administration ; Intensive Care Units/organization & administration ; Kidney Failure, Chronic/diagnosis ; Kidney Failure, Chronic/epidemiology ; Kidney Failure, Chronic/therapy ; Male ; Middle Aged ; New York City ; Outcome Assessment, Health Care ; Pandemics ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/therapy ; Prevalence ; Renal Dialysis/methods ; Renal Dialysis/mortality ; Retrospective Studies ; Risk Assessment ; Severity of Illness Index ; Sex Factors ; Statistics, Nonparametric ; Survival Analysis ; Vulnerable Populations/statistics & numerical data
    Keywords covid19
    Language English
    Publishing date 2020-05-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.2020040470
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  8. Article ; Online: Immunoglobulin-Negative DNAJB9-Associated Fibrillary Glomerulonephritis: A Report of 9 Cases.

    Said, Samar M / Rocha, Alejandro Best / Royal, Virginie / Valeri, Anthony M / Larsen, Christopher P / Theis, Jason D / Vrana, Julie A / McPhail, Ellen D / Bandi, Lalitha / Safabakhsh, Saied / Barnes, Chadwick / Cornell, Lynn D / Fidler, Mary E / Alexander, Mariam Priya / Leung, Nelson / Nasr, Samih H

    American journal of kidney diseases : the official journal of the National Kidney Foundation

    2020  Volume 77, Issue 3, Page(s) 454–458

    Abstract: Fibrillary glomerulonephritis (FGN) was previously defined by glomerular deposition of haphazardly oriented fibrils that stain with antisera to immunoglobulins but do not stain with Congo red. We report what is to our knowledge the first series of ... ...

    Abstract Fibrillary glomerulonephritis (FGN) was previously defined by glomerular deposition of haphazardly oriented fibrils that stain with antisera to immunoglobulins but do not stain with Congo red. We report what is to our knowledge the first series of immunoglobulin-negative FGN, consisting of 9 adults (7 women and 2 men) with a mean age at diagnosis of 66 years. Patients presented with proteinuria (100%; mean protein excretion, 3g/d), hematuria (100%), and elevated serum creatinine level (100%). Comorbid conditions included carcinoma in 3 and hepatitis C virus infection in 2; no patient had hypocomplementemia or monoclonal gammopathy. Histologically, glomeruli were positive for DNAJB9, showed mostly mild mesangial hypercellularity and/or sclerosis, and were negative for immunoglobulins by immunofluorescence on frozen and paraffin tissue. Ultrastructurally, randomly oriented fibrils measuring 13 to 20nm in diameter were seen intermingling with mesangial matrix in all and infiltrating glomerular basement membranes in 5. On follow-up (mean duration, 21 months), 2 had disease remission, 4 had persistently elevated serum creatinine levels and proteinuria, and 3 required kidney replacement therapy. Thus, rare cases of FGN are not associated with glomerular immunoglobulin deposition, and the diagnosis of FGN in these cases can be confirmed by DNAJB9 immunostaining. Pathogenesis remains to be elucidated.
    MeSH term(s) Aged ; Aged, 80 and over ; Comorbidity ; Creatinine/metabolism ; Female ; Glomerular Basement Membrane/ultrastructure ; Glomerular Mesangium/ultrastructure ; Glomerulonephritis/epidemiology ; Glomerulonephritis/metabolism ; Glomerulonephritis/pathology ; Glomerulonephritis/therapy ; HSP40 Heat-Shock Proteins/metabolism ; Hematuria/metabolism ; Humans ; Immunoglobulin G/metabolism ; Immunosuppressive Agents/therapeutic use ; Liver Cirrhosis/epidemiology ; Male ; Membrane Proteins/metabolism ; Microscopy, Electron ; Middle Aged ; Molecular Chaperones/metabolism ; Neoplasms/epidemiology ; Proteinuria/metabolism ; Pulmonary Disease, Chronic Obstructive/epidemiology ; Renal Replacement Therapy ; Sclerosis
    Chemical Substances DNAJB9 protein, human ; HSP40 Heat-Shock Proteins ; Immunoglobulin G ; Immunosuppressive Agents ; Membrane Proteins ; Molecular Chaperones ; Creatinine (AYI8EX34EU)
    Language English
    Publishing date 2020-07-23
    Publishing country United States
    Document type Research Support, Non-U.S. Gov't
    ZDB-ID 604539-x
    ISSN 1523-6838 ; 0272-6386
    ISSN (online) 1523-6838
    ISSN 0272-6386
    DOI 10.1053/j.ajkd.2020.04.015
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  9. Article ; Online: The characteristics of patients with kidney light chain deposition disease concurrent with light chain amyloidosis.

    Said, Samar M / Best Rocha, Alejandro / Valeri, Anthony M / Paueksakon, Paisit / Dasari, Surendra / Theis, Jason D / Vrana, Julie A / Obadina, Modupe O / Saghafi, Darius / Alexander, Mariam Priya / Sethi, Sanjeev / Larsen, Christopher P / Joly, Florent / Dispenzieri, Angela / Bridoux, Frank / Sirac, Christophe / Leung, Nelson / Fogo, Agnes B / McPhail, Ellen D /
    Nasr, Samih H

    Kidney international

    2021  Volume 101, Issue 1, Page(s) 152–163

    Abstract: The type of monoclonal light chain nephropathy is thought to be largely a function of the structural and physiochemical properties of light chains; hence most affected patients have only one light chain kidney disease type. Here, we report the first ... ...

    Abstract The type of monoclonal light chain nephropathy is thought to be largely a function of the structural and physiochemical properties of light chains; hence most affected patients have only one light chain kidney disease type. Here, we report the first series of kidney light chain deposition disease (LCDD) concomitant with light chain amyloidosis (LCDD+AL), with or without light chain cast nephropathy (LCCN). Our LCDD+AL cohort consisted of 37 patients (54% females, median age 70 years (range 40-86)). All cases showed Congo red-positive amyloid deposits staining for one light chain isotype on immunofluorescence (62% lambda), and LCDD with diffuse linear staining of glomerular and tubular basement membranes for one light chain isotype (97% same isotype as the amyloidogenic light chain) and ultrastructural non-fibrillar punctate deposits. Twelve of 37 cases (about 1/3 of patients) had concomitant LCCN of same light chain isotype. Proteomic analysis of amyloid and/or LCDD deposits in eight revealed a single light chain variable domain mutable subgroup in all cases (including three with separate microdissections of LCDD and amyloid light chain deposits). Clinical data on 21 patients showed proteinuria (100%), hematuria (75%), kidney insufficiency and nephrotic syndrome (55%). Extra-kidney involvement was present in 43% of the patients. Multiple myeloma occurred in 68% (about 2/3) of these patients; none had lymphoma. On follow up (median 16 months), 63% developed kidney failure and 56% died. The median kidney and patient survivals were 12 and 32 months, respectively. LCDD+AL mainly affected patients 60 years of age or older. Thus, LCDD+AL could be caused by two pathological light chains produced by subclones stemming from one immunoglobulin light chain lambda or kappa rearrangement, with a distinct mutated complementary determining region.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Amyloidosis/complications ; Amyloidosis/diagnosis ; Amyloidosis/pathology ; Female ; Humans ; Immunoglobulin Light Chains ; Kidney/pathology ; Kidney Diseases/complications ; Kidney Diseases/etiology ; Male ; Middle Aged ; Multiple Myeloma/complications ; Proteomics
    Chemical Substances Immunoglobulin Light Chains
    Language English
    Publishing date 2021-11-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2021.10.019
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  10. Article ; Online: Pathological characteristics of light chain crystalline podocytopathy.

    Nasr, Samih H / Kudose, Satoru / Javaugue, Vincent / Harel, Stéphanie / Said, Samar M / Pascal, Virginie / Stokes, M Barry / Vrana, Julie A / Dasari, Surendra / Theis, Jason D / Osuchukwu, George A / Sathick, Insara Jaffer / Das, Arjun / Kashkouli, Ali / Suchin, Elliot J / Liss, Yaakov / Suldan, Zalman / Verine, Jerome / Arnulf, Bertrand /
    Talbot, Alexis / Sethi, Sanjeev / Zaidan, Mohamad / Goujon, Jean-Michel / Valeri, Anthony M / Mcphail, Ellen D / Sirac, Christophe / Leung, Nelson / Bridoux, Frank / D'Agati, Vivette D

    Kidney international

    2022  Volume 103, Issue 3, Page(s) 616–626

    Abstract: Monoclonal immunoglobulin light chain (LC) crystalline inclusions within podocytes are rare, poorly characterized entities. To provide more insight, we now present the first clinicopathologic series of LC crystalline podocytopathy (LCCP) encompassing 25 ... ...

    Abstract Monoclonal immunoglobulin light chain (LC) crystalline inclusions within podocytes are rare, poorly characterized entities. To provide more insight, we now present the first clinicopathologic series of LC crystalline podocytopathy (LCCP) encompassing 25 patients (68% male, median age 56 years). Most (80%) patients presented with proteinuria and chronic kidney disease, with nephrotic syndrome in 28%. Crystalline keratopathy and Fanconi syndrome were present in 22% and 10%, respectively. The hematologic condition was monoclonal gammopathy of renal significance (MGRS) in 55% and multiple myeloma in 45%. The serum monoclonal immunoglobulin was IgG κappa in 86%. Histologically, 60% exhibited focal segmental glomerulosclerosis (FSGS), often collapsing. Ultrastructurally, podocyte LC crystals were numerous with variable effacement of foot processes. Crystals were also present in proximal tubular cells as light chain proximal tubulopathy (LCPT) in 80% and in interstitial histiocytes in 36%. Significantly, frozen-section immunofluorescence failed to reveal the LC composition of crystals in 88%, requiring paraffin-immunofluorescence or immunohistochemistry, with identification of kappa LC in 87%. The LC variable region gene segment, determined by mass spectrometry of glomeruli or bone marrow plasma cell sequencing, was IGKV1-33 in four and IGKV3-20 in one. Among 21 patients who received anti-plasma cell-directed chemotherapy, 50% achieved a kidney response, which depended on a deep hematologic response. After a median follow-up of 36 months, 26% progressed to kidney failure and 17% died. The mean kidney failure-free survival was 57.6 months and was worse in those with FSGS. In sum, LCCP is rare, mostly associates with IgG κappa MGRS, and frequently has concurrent LCPT, although Fanconi syndrome is uncommon. Paraffin-immunofluorescence and electron microscopy are essential to prevent misdiagnosis as primary FSGS since kidney survival depends on early diagnosis and subsequent clone-directed therapy.
    MeSH term(s) Humans ; Male ; Middle Aged ; Female ; Glomerulosclerosis, Focal Segmental/pathology ; Fanconi Syndrome/pathology ; Paraffin ; Kidney/pathology ; Kidney Diseases/pathology ; Renal Insufficiency/pathology ; Immunoglobulin G
    Chemical Substances Paraffin (8002-74-2) ; Immunoglobulin G
    Language English
    Publishing date 2022-12-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2022.11.026
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