Publications by authors named "Jolanta Kowalewska"

44 Publications

Educational Case: Giant Cell Tumor of the Bone in Both the Axial and Appendicular Skeleton.

Acad Pathol 2021 Jan-Dec;8:23742895211008657. Epub 2021 Apr 9.

Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA, USA.

http://journals.sagepub.com/doi/10.1177/2374289517715040..
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/23742895211008657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040597PMC
April 2021

Fibrilo-Tactoid Glomerulonephritis: A Possible Novel Morphological Variant.

Case Rep Nephrol Dial 2020 Sep-Dec;10(3):154-162. Epub 2020 Nov 17.

Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, Virginia, USA.

Fibrillary and immunotactoid glomerulonephritis are infrequent causes of primary nephrotic range proteinuria and are poorly understood. Recent significant developments include the discovery of DNA JB9 antigen in fibrillary glomerulonephritis. Here, we present a case of a middle-aged woman who presented with nephrotic range proteinuria, hematuria, and normal renal function. Renal biopsy revealed fibrils that were randomly arranged on electron microscopy. They were of small size and congo red negative similar to the ones found in fibrillary glomerulonephritis, but were also DNA JB 9 negative, and had a hollow core like in immunotactoid glomerulopathy. Though we try to classify these conditions into either immunotactoid glomerulonephropathy (ITGN) or fibrillary glomerulonephritis (FGN), there are scenarios such as this case where it does not fit into either and is probably an overlap or intermediate variant of these two conditions. Pathological features of these glomerulonephrites are discussed together with their clinical implications, treatment choices, and diagnostic importance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000510871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747065PMC
November 2020

Previously Unidentified Gene Variation Associated with Fabry Disease: The Impact on One Family.

Case Rep Nephrol 2020 19;2020:8899703. Epub 2020 Sep 19.

Division of Nephrology, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA, USA.

Fabry disease is an X-linked lysosomal storage genetic disorder associated with over 1000 mutations in the gene region. We report here a 69-year-old male who underwent a kidney biopsy to evaluate progressive renal failure. He was found to have zebra bodies in visceral epithelial cells on biopsy, with electron microscopy showing inclusions within the cytoplasm of multiple podocytes consistent with Fabry disease. An alpha-galactosidase level was found to be 21 nm/hr/mg (normal range 50-150 nm/hr/mg). Genetic studies revealed a missense variant in the gene with alanine replaced by cysteine at position 682 (c.682 A > C, p.N228H) that had not been previously associated with Fabry disease. The same variant was detected in two additional family members. The pathologic findings, clinical features, and low alpha-galactosidase level suggest that the c.682 A > C variant is associated with Fabry disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/8899703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520668PMC
September 2020

Educational Case: Nephrotic Syndrome in Older Adult.

Acad Pathol 2020 Jan-Dec;7:2374289520944554. Epub 2020 Aug 18.

Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA, USA.

http://journals.sagepub.com/doi/10.1177/2374289517715040..
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2374289520944554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436787PMC
August 2020

Comment: Newly Diagnosed Glomerulonephritis During COVID-19 Infection Undergoing Immunosuppression Therapy, a Case Report.

Iran J Kidney Dis 2020 07;14(4):323-325

Department of Nephropathology, Nickan Research Institute, Isfahan, Iran.

View Article and Find Full Text PDF

Download full-text PDF

Source
July 2020

Corrigendum to "Pericardial Tamponade: An Uncommon Clinical Presentation in cANCA Related Vasculitis and Glomerulonephritis in Association with Very High Titres of ANA".

Case Rep Nephrol 2019;2019:6703652. Epub 2019 Aug 22.

Department of Nephrology, Eastern Virginia Medical School, 855 W Brambleton Ave., Norfolk, VA 23510, USA.

[This corrects the article DOI: 10.1155/2019/4983139.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/6703652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724443PMC
August 2019

Transplantation With APOL1 Risk Variant Kidney May Be Associated With Lifetime Risk for Recurrence of Focal Segmental Glomerulosclerosis: A Case Report and Review of Literature.

Transplant Proc 2019 Nov 16;51(9):3077-3079. Epub 2019 Jul 16.

Nephrology Department, Eastern Virginia Medical School, Norfolk, Virginia.

The APOL1 gene mutation is increasingly recognized as an import factor in living kidney donation. APOL1 gene variants prevalent in the African American population have been associated with increased risk of glomerulopathy. Shorter allograft survival is seen in transplants from donors who had 2 risk APOL1 gene alleles. In the early posttransplant period, kidneys with 2 risk alleles of APOL1 had higher risk of graft loss compared to 1 or 0 risk alleles, but by year 4 of transplant it was almost similar. The authors have suggested that recipients of kidney transplants with 2 risk alleles may only be at risk for kidney failure during the early initial period. We present here a case of a patient with 2 risk APOL1 alleles who received renal transplant from her identical twin and developed glomerulopathy 18 years after the transplant. No case of APOL1-associated recurrent glomerulonephritis has been described in a recipient after 10 years. This suggests that the risk of recurrence of glomerulopathy in allograft transplants with 2 risk allele variants may not be limited to the initial post-transplant period; rather, it may be a lifetime risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.transproceed.2019.04.056DOI Listing
November 2019

Pericardial Tamponade: An Uncommon Clinical Presentation in cANCA Related Vasculitis and Glomerulonephritis in Association with Very High Titres of ANA.

Case Rep Nephrol 2019 13;2019:4983139. Epub 2019 Jun 13.

Nephrology, Eastern Virginia Medical School, 855 W Brambelton Ave, Norfolk, VA 23510, USA.

ANCA (anti-neutrophil cytoplasmic antibody) vasculitides are systemic autoimmune diseases in which anti-neutrophilic cytoplasmic antibodies activate primed neutrophils, thereby generating an inflammatory cascade resulting in the damage of small sized blood vessels in various organs of the body, including the heart. Pleuropericardial involvement is underrecognized as a complication of ANCA vasculitis and is highlighted in this case report of a 51-year-old male who presented with an initial symptomatic presentation of pleuropericardial effusion progressing to pericardial tamponade in the setting of a later renal biopsy proven pauci-immune crescentic glomerulonephritis with high ANA titres along with positive cANCA (cytoplasmic ANCA) and PR3 (proteinase 3) antibodies. He was found to have acute renal failure which progressively got better with cyclophosphamide.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/4983139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595352PMC
June 2019

ANCA-Associated Vasculitis Co-Occurrence With Systemic Sclerosis: A Case Report of a Rare Diagnostic Dilemma.

J Investig Med High Impact Case Rep 2018 Jan-Dec;6:2324709618785188. Epub 2018 Jun 28.

Eastern Virginia Medical School, Norfolk, VA, USA.

Systemic sclerosis (SSc) is a rare autoimmune disorder that is typically divided into limited cutaneous systemic sclerosis and diffuse cutaneous systemic sclerosis. Scleroderma renal crisis (SRC) is a severe complication of SSc and typically presents with new-onset hypertension and a reduction in renal functioning. In patients presenting with typical features of SRC, treatment with an angiotensin-converting enzyme inhibitor along with dialysis as needed is typically initiated empirically. Renal biopsy is not recommended in patients with SSc presenting with typical features of SRC. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare co-occurrence with SSc, in around 2.5% to 9% of patients. AAV is an inflammatory condition that can result in renal failure due to mononuclear cell infiltration and destruction of blood vessels. Treatment of AAV is drastically different from SRC and typically consists of immunosuppressants and dialysis if needed. SRC and AAV can only reliably be distinguished by renal biopsy. We present a rare case of a 70-year-old female with limited cutaneous systemic sclerosis who presented to the emergency department with new-onset renal failure. Her serology was found to be positive for antinuclear antibodies and myeloperoxidase antibodies, resulting in a renal biopsy, which revealed an acute necrotizing vasculitis consistent with AAV. We suggest consideration of a renal biopsy in patients with SSc who present with new-onset renal failure, especially with nonresponse to SRC treatment or positive serology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2324709618785188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062775PMC
June 2018

Clinicopathologic correlations of renal pathology in the adult population of Poland.

Nephrol Dial Transplant 2017 Apr;32(suppl_2):ii209-ii218

Zaklad Etyki i Filozofii Czlowieka, Uniwersytet Medyczny w Lublinie, Lublinie, Poland.

Background: This is the first report on the epidemiology of biopsy-proven kidney diseases in Poland.

Methods: The Polish Registry of Renal Biopsies has collected information on all (n = 9394) native renal biopsies performed in Poland from 2009 to 2014. Patients' clinical data collected at the time of biopsy, and histopathological diagnoses were used for epidemiological and clinicopathologic analysis.

Results: There was a gradual increase in the number of native renal biopsies performed per million people (PMP) per year in Poland in 2009-14, starting from 36 PMP in 2009 to 44 PMP in 2014. A considerable variability between provinces in the mean number of biopsies performed in the period covered was found, ranging from 5 to 77 PMP/year. The most common renal biopsy diagnoses in adults were immunoglobulin A nephropathy (IgAN) (20%), focal segmental glomerulosclerosis (FSGS) (15%) and membranous glomerulonephritis (MGN) (11%), whereas in children, minimal change disease (22%), IgAN (20%) and FSGS (10%) were dominant. Due to insufficient data on the paediatric population, the clinicopathologic analysis was limited to patients ≥18 years of age. At the time of renal biopsy, the majority of adult patients presented nephrotic-range proteinuria (45.2%), followed by urinary abnormalities (38.3%), nephritic syndrome (13.8%) and isolated haematuria (1.7%). Among nephrotic patients, primary glomerulopathies dominated (67.6% in those 18-64 years of age and 62.4% in elderly patients) with leading diagnoses being MGN (17.1%), FSGS (16.2%) and IgAN (13.0%) in the younger cohort and MGN (23.5%), amyloidosis (18.8%) and FSGS (16.8%) in the elderly cohort. Among nephritic patients 18-64 years of age, the majority (55.9%) suffered from primary glomerulopathies, with a predominance of IgAN (31.3%), FSGS (12.7%) and crescentic GN (CGN) (11.1%). Among elderly nephritic patients, primary and secondary glomerulopathies were equally common (41.9% each) and pauci-immune GN (24.7%), CGN (20.4%) and IgAN (14.0%) were predominant. In both adult cohorts, urinary abnormalities were mostly related to primary glomerulopathies (66.8% in younger and 50% in elderly patients) and the leading diagnoses were IgAN (31.4%), FSGS (15.9%), lupus nephritis (10.7%) and FSGS (19.2%), MGN (15.1%) and pauci-immune GN (12.3%), respectively. There were significant differences in clinical characteristics and renal biopsy findings between male and female adult patients.

Conclusions: The registry data focused new light on the epidemiology of kidney diseases in Poland. These data should be used in future follow-up and prospective studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfw365DOI Listing
April 2017

Single center experience of subclinical rejections and BK nephropathies by kidney allografts' surveillance biopsies.

Adv Med Sci 2017 Mar 24;62(1):110-115. Epub 2017 Feb 24.

1st Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Bialystok, Poland.

Purpose: Acute rejection of the kidney allograft remains the most important factor affecting the long-term graft outcome and is a major predictor of development of chronic damage and graft loss. Several studies have shown that early detection and treatment of subclinical rejection episodes may be beneficial for the graft outcome. The role of protocol (surveillance) biopsies and the value of donor specific antibodies (DSA) monitoring are still debatable.

Methods: This is a prospective observational study involving seventeen kidney recipients transplanted in north-eastern part of Poland who underwent "zero", 3-month and 12-month allograft biopsies as well as DSA assessment.

Results: Histologic analysis of the biopsies showed subclinical acute cellular rejection in 17.6% of patients (two tubulointerstitial, one vascular) at 3-months post transplantation, and additional case of borderline rejection at the 12-month point. Moreover, two cases (11.8%) of polyomavirus BK nephropathy were diagnosed (one at 3 and one at 12 month point). None of the patients developed de novo DSA.

Conclusions: Our protocol biopsies allowed us to detect significant proportion of patients with subclinical, but histologically relevant acute cellular rejection and BK nephropathy. Early therapeutic intervention had beneficial effects in a 4-year follow up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.advms.2016.07.005DOI Listing
March 2017

Kidney Biopsies May Help Predict Renal Function After Liver Transplantation.

Transplantation 2016 10;100(10):2122-8

1 Departments of Medicine, Pathology and Surgery, University of Washington, Seattle, WA.

Background: Renal biopsy has been proposed to determine the cause or reversibility of renal failure for patients with end-stage liver disease and may be useful in the kidney allocation. Nevertheless, little data exist to validate the usefulness of kidney biopsies in this patient population.

Methods: We evaluated the utility of renal biopsies in a cohort of 59 consecutive liver transplant candidates with renal impairment of unclear etiology referred to determine the need for simultaneous liver kidney transplantation (SLK) versus liver alone transplantation (LAT). Pathological diagnoses, patient outcomes and the usefulness of biopsy results in predicting renal recovery were analyzed.

Results: Our biopsy complication rate was relatively low with only 2.9% and 4.2% serious complications occurring with transjugular and percutaneous renal biopsies, respectively. The most common pathological diagnoses on renal biopsies were membranoproliferative glomerulonephritis (23%) followed by IgA nephropathy (19%) and acute tubular injury (19%). Simultaneous liver kidney transplantation was recommended for patients with greater than 40% global glomerular sclerosis, or with interstitial fibrosis greater than 30% or for patients on hemodialysis for 2 months or longer. The best histological predictor for posttransplant glomerular filtration rate in the LAT group was the extent of global glomerulosclerosis (P = 0.0001). Based on biopsy criteria, we were able to avoid kidney allocation to 70% of our patients with renal dysfunction. Over the first year posttransplant, SLK and LAT patients had comparable estimated glomerular filtration rates. Kaplan-Meier survival analysis did not demonstrate a difference in patient survival between patients who underwent LAT versus SLK.

Conclusions: Renal biopsy can be relatively safe in this population, may help elucidate the etiology of renal failure, may predict post-LAT kidney function, and may be helpful in kidney allocation for liver transplant candidates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000001334DOI Listing
October 2016

Pathology of recurrent diseases in kidney allografts: membranous nephropathy and focal segmental glomerulosclerosis.

Curr Opin Organ Transplant 2013 Jun;18(3):313-8

Department of Pathology, Medical University of Bialystok, Bialystok, Poland.

Purpose Of Review: Glomerulonephritis is the leading cause of end-stage renal failure in renal transplant recipients. Recurrence of diseases in kidney allograft provides a unique opportunity to study the mechanisms of kidney disorders leading to the underlying native organ failure. There have been new advances in the understanding of the mechanisms of membranous nephropathy and focal segmental glomerulosclerosis (FSGS).

Recent Findings: Recent studies of recurrent membranous nephropathy provide evidence of the presence of circulating recipient factor that targets the donor kidney and put forward the evidence of antiphospholipase A2 receptor antibody pathogenicity in some cases, point to a different pathogenesis of recurrent and de-novo membranous nephropathy, and stress the importance of early morphologic recognition of recurrent membranous nephropathy. New advances in understanding the FSGS include identification of soluble podocyte urokinase receptor as a circulating factor leading to the development and recurrence of FSGS after transplantation, imply that podocyte injury may be a reversible lesion, and suggest a dual role of activated parietal epithelial cells in sclerosing glomerular injury as well as in regeneration and repair.

Summary: Several new mechanisms of glomerular injury have been implicated in the development of recurrent kidney diseases. When further confirmed, some of these might result in early diagnosis and development of better therapy of the respective disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MOT.0b013e3283614ab5DOI Listing
June 2013

Expression of estrogen receptors α and β in paratesticular tissues in boys operated on for unilateral cryptorchidism between the 1st and 4th years of life.

Med Sci Monit 2012 Oct;18(10):CR630-4

Department of Pediatric Surgery Medical University of Bialystok, Bialystok, Poland.

Background: The aim of this study was to assess the expression of estrogen receptors alpha and beta in paratesticular tissues in a group of boys with and without cryptorchidism, and evaluation of karyotypes, localization, morphology and the major length of the undescended testes.

Material/methods: Fifty boys (1-4 years old) with unilateral cryptorchidism were evaluated. Fifty healthy boys within the same age range, with inguinal hernia, served as a control group. Measurements concerning expression of ERalpha ERbeta receptors were preformed using monoclonal mouse antibodies against human receptor alpha and beta.

Results: In the mesothelial layer, the expression of ERalpha was higher in the patients group with undescended testes and it was statistically significant (p=0.04). There was no difference in the expression of ERbeta in this layer between groups. In the stromal cell layer there was statistically significant higher expression of ERbeta (p<0.05) in the group of patients with undescended testes.

Conclusions: There was no difference between expressions of ERalpha in stromal cell layer. In the endothelial layer there was no difference in expression of ERalpha and ERbeta. In the smooth muscle layer there was no expression of ERalpha in either group. The expression of ERbeta in the smooth muscle layer was nearly identical in both groups. Undescended testes were generally found in the superficial inguinal pouch (n=46). The major lengths of the undescended testes were smaller in comparison to the testes positioned normally. In 9 of the cases the testes had different shape, and turgor deficit, and epididymides were smaller, dysplastic and separated from the testis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560562PMC
http://dx.doi.org/10.12659/msm.883490DOI Listing
October 2012

Bone as a source of organism vitality and regeneration.

Folia Histochem Cytobiol 2011 ;49(4):558-69

State Research Institute Center for Innovative Medicine, Vilnius, Lithuania.

The most important features that determine the vital role of bone include: a) a continuous supply of calcium, which is indispensible for every cell of the entire organism at all times, and b) the delivery of circulating blood cells and some adult stem cells to keep the body vigorous, ready for self-reparation, and continuously rebuilding throughout life. These functions of bones are no less important than protecting the body cavities, serving as mechanical levers connected to the muscles, and determining the shape and dimensions of the entire organism. The aim of this review was to address some basic cellular and molecular knowledge to better understand the complex interactions of bone structural components. The apprehension of osteoblast differentiation and its local regulation has substantially increased in recent years. It has been suggested that osteocytes, cells within the bone matrix, act as regulatory mechanosensors. Therefore immobility as well as limited activity has a dramatic effect on bone structure and influences a broad spectrum of bone physiology-related functions as well as the functions of many other organs. Lifelong bone rebuilding is modulated through several pathways, including the Wnt pathway that regulates bone formation and resorption. In the adult skeleton, bone is continuously renewed in response to a variety of stimuli, such as the specific process of remodeling dependent on RANK/ /RANKL/OPG interactions. Better understanding of bone biology provides opportunities for the development of more effective prevention and treatment modalities for a variety of bone diseases, including new approaches to adult stem cell-based therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5603/fhc.2011.0079DOI Listing
May 2013

Cryoglobulinemic glomerulonephritis--lessons from animal models.

Folia Histochem Cytobiol 2011 ;49(4):537-46

Department of Medical Pathomorphology, Medical University of Bialystok, Poland.

In humans cryoglobulinemic glomerulonephritis (CGGN) may develop in the course of systemic cryoglobulinemia (CG) and is often associated with hepatitis C virus infection. It is believed that the glomerular injury in CG results from the deposition of immune complexes, but exact sequence of events in this process is unknown. Experimental models of CGGN provide an important tool to study pathogenesis of this type injury. This review describes two mouse models of CGGN and their use in understanding the role of various molecules involved in regulation of inflammatory and fibrosis pathways, such as complement components, Fc receptors, growth factors, and others; as well as illustrates their role in testing novel approaches of treatment in this type of renal injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5603/fhc.2011.0077DOI Listing
May 2013

Role of smooth muscle protein SM22α in glomerular epithelial cell injury.

Am J Physiol Renal Physiol 2011 Apr 2;300(4):F1026-42. Epub 2011 Feb 2.

Div. of Nephrology, Department of Medicine, Univ. of Washington, Seattle, WA 98195, USA.

Podocytes are considered terminally differentiated cells in the mature kidney under normal conditions. In the face of injury, podocytes may proceed along several possible pathways, including dedifferentiation and proliferation, persistent cell cycle arrest, hypertrophy, apoptosis, or necrosis. There is mounting evidence that transdifferentiation into a dysregulated phenotype may also be a potential cell fate. We have previously reported that the transcript of SM22α, an actin-binding protein considered one of the earliest markers of smooth muscle differentiation, is upregulated nearly 70-fold in glomeruli of rats with passive Heymann nephritis (PHN). In contrast, the SM22α transcript is absent in normal adult rat glomeruli. The purpose of this study was to define SM22α's expression during kidney development and its role in glomerular diseases characterized by podocyte injury and proteinuria. During glomerulogenesis and podocyte differentiation, SM22α was expressed in glomeruli. This expression disappeared with glomerular maturation. Along with SM22α induction in PHN, confirmed at both mRNA and protein levels, SM22α was also induced across a broad range of proteinuric diseases, including experimental animal models (puromycin aminonucleoside nephropathy, adriamycin nephropathy, passive nephrotoxic nephritis, and diet-induced obesity) and human diseases (collapsing glomerulopathy, diabetic nephropathy, classic focal segmental glomerulosclerosis, IgA nephropathy, minimal-change disease, membranous nephropathy, and membranoproliferative glomerulonephritis). Crescentic glomerulonephritis was induced in SM22α +/+ and SM22α -/- mice by intraperitoneal injection of sheep anti-rabbit glomeruli antibody 12.5 mg/20 g body wt × 2 doses (n = 12-15/group), with mice euthanized at 7 and 14 days. Compared with SM22α -/- mice, SM22α +/+ mice demonstrated worse disease by histopathological parameters. In addition, there was greater apoptosis (cleaved caspase-3 immunostaining), fewer podocytes (Wilms' tumor-1 immunostaining), and less proliferation (Ki-67 immunostaining) in diseased SM22α +/+ mice. Furthermore, there was decreased activation of Erk1/2 in diseased SM22α +/+ mice. We conclude that the de novo expression of SM22α in glomerular epithelial cells affects the course of crescentic glomerulonephritis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajprenal.00187.2010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074994PMC
April 2011

Patterns of glomerular injury in kidneys infiltrated by lymphoplasmacytic neoplasms.

Hum Pathol 2011 Jun 1;42(6):896-903. Epub 2011 Feb 1.

Department of Pathology, University of Washington, Seattle, WA 98195, USA.

Glomerular injury may occur as a result of immune dysfunction in patients with remote lymphoplasmacytic neoplasms. Glomerular injury concurrent with direct infiltration of the kidney by lymphoplasmacytic neoplasms has been reported but is not extensively characterized. We identified 18 patients, all presenting with elevated serum creatinine and many with proteinuria, whose renal biopsies showed direct involvement of kidney by a variety of neoplasms, including chronic leukocytic leukemia/small lymphocytic lymphoma (n = 7), diffuse large B-cell lymphoma (n = 6), multiple myeloma (n = 4), or B-cell lymphoblastic lymphoma (n = 1). In 10 cases (55%), there was coexistent glomerular pathology: 5 of these cases, including glomerulonephritis with membranoproliferative glomerulonephritis-like pattern of injury (n = 4) and membranous nephropathy (n = 1), featured deposition of immune complexes; 2 demonstrated deposition of monoclonal immunoglobulin components: λ light chain amyloidosis (n = 1) and light chain deposition disease (n = 1); 2 showed minimal change disease; and, in 1 case, there was focal crescentic pauci-immune-type glomerulonephritis. In addition, 1 biopsy revealed diabetic nephropathy and 3 showed nonspecific ischemic changes. In the remaining 4 cases, there were no significant glomerular abnormalities. In 11 cases (61%), the diagnosis of lymphoproliferative disease was established following the kidney biopsy. Our study indicates that lymphoplasmacytic neoplasms may be first diagnosed in renal biopsies performed for evaluation of renal dysfunction with or without proteinuria. Concurrent glomerular injury may be a direct result of the lymphoplasmacytic disorder through a paraprotein deposition process resulting in amyloid or monoclonal immunoglobulin deposition disease, or may be caused indirectly through immune-mediated mechanisms, as in the cases of glomerulonephritis with membranoproliferative glomerulonephritis-like pattern of injury, membranous nephropathy, and possibly minimal change disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.humpath.2010.09.009DOI Listing
June 2011

Temporal small-vessel inflammation in patients with giant cell arteritis: clinical course and preliminary immunohistopathologic characterization.

J Rheumatol 2011 Feb 1;38(2):331-8. Epub 2010 Dec 1.

Division of Rheumatology, Allergy and Immunology, Winthrop University Hospital, 120 Mineola Blvd., Suite 410, Mineola, New York 11501, USA.

Objective: To investigate the occurrence, clinical correlates, and immunohistochemical phenotype of temporal small-vessel inflammation (TSVI) in temporal artery biopsies from patients presenting with clinical features of giant cell arteritis (GCA).

Methods: We retrospectively reviewed 41 temporal artery biopsy specimens for the presence of inflammatory infiltrates in small vessels external to the temporal artery adventitia (TSVI); 33 had sufficient clinical and pathological data for detailed analysis. Clinical and laboratory features at presentation and corticosteroid treatment patterns of patients with isolated TSVI were compared to those of patients with positive and negative biopsies. The cellular composition of the infiltrates was further characterized by immunohistochemistry.

Results: Twenty-three (70%) specimens had evidence of TSVI including 10 with concurrent GCA and 13 (39%) with isolated TSVI. TSVI was found in all positive temporal artery biopsies. The proportion of macrophages and of lymphocyte subpopulations differed between infiltrates observed in TSVI and those of the main temporal artery wall. Initial erythrocyte sedimentation rate (ESR) was similar in the TSVI and positive biopsy groups and was significantly higher than in the negative biopsy group. Patients with isolated TSVI more often had symptoms of polymyalgia rheumatica compared to the positive biopsy group. Patients with TSVI received corticosteroid doses that were intermediate between patients with positive and those with negative biopsies.

Conclusion: A significant number of patients with clinical features of GCA demonstrated isolated TSVI. Differences in the clinical presentation and cellular composition suggest that TSVI may represent a subset of GCA and should be considered in the interpretation of temporal artery biopsies and treatment decisions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3899/jrheum.100455DOI Listing
February 2011

BTBR Ob/Ob mutant mice model progressive diabetic nephropathy.

J Am Soc Nephrol 2010 Sep 15;21(9):1533-42. Epub 2010 Jul 15.

Department of Pathology, University of Washington, Seattle, Washington, USA.

There remains a need for robust mouse models of diabetic nephropathy (DN) that mimic key features of advanced human DN. The recently developed mouse strain BTBR with the ob/ob leptin-deficiency mutation develops severe type 2 diabetes, hypercholesterolemia, elevated triglycerides, and insulin resistance, but the renal phenotype has not been characterized. Here, we show that these obese, diabetic mice rapidly develop morphologic renal lesions characteristic of both early and advanced human DN. BTBR ob/ob mice developed progressive proteinuria beginning at 4 weeks. Glomerular hypertrophy and accumulation of mesangial matrix, characteristic of early DN, were present by 8 weeks, and glomerular lesions similar to those of advanced human DN were present by 20 weeks. By 22 weeks, we observed an approximately 20% increase in basement membrane thickness and a >50% increase in mesangial matrix. Diffuse mesangial sclerosis (focally approaching nodular glomerulosclerosis), focal arteriolar hyalinosis, mesangiolysis, and focal mild interstitial fibrosis were present. Loss of podocytes was present early and persisted. In summary, BTBR ob/ob mice develop a constellation of abnormalities that closely resemble advanced human DN more rapidly than most other murine models, making this strain particularly attractive for testing therapeutic interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1681/ASN.2009121290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3013527PMC
September 2010

Combination of peritubular c4d and transplant glomerulopathy predicts late renal allograft failure.

J Am Soc Nephrol 2009 Oct 3;20(10):2260-8. Epub 2009 Sep 3.

Department of Medicine, Division of Nephrology,University of Washington, Seattle, Washington 98195-6521, USA.

The histologic associations and clinical implications of peritubular capillary C4d staining from long-term renal allografts are unknown. We identified 99 renal transplant patients who underwent an allograft biopsy for renal dysfunction at least 10 yr after transplantation, 25 of whom were C4d-positive and 74 of whom were C4d-negative. The average time of the index biopsy from transplantation was 14 yr in both groups. Compared with C4d-negative patients, C4d-positive patients were younger at transplantation (29 +/- 13 versus 38 +/- 12 yr; P < 0.05) and were more likely to have received an allograft from a living donor (65 versus 35%; P < 0.001). C4d-positive patients had more inflammation, were more likely to have transplant glomerulopathy, and had worse graft outcome. The combined presence of C4d positivity, transplant glomerulopathy, and serum creatinine of >2.3 mg/dl at biopsy were very strong predictors of rapid graft loss. C4d alone did not independently predict graft loss. Retrospective staining of historical samples from C4d-positive patients demonstrated C4d deposition in the majority of cases. In summary, these data show that in long-term renal allografts, peritubular capillary staining for C4d occurs in approximately 25% of biopsies, can persist for many years after transplantation, and strongly predicts graft loss when combined with transplant glomerulopathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1681/ASN.2009020199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754096PMC
October 2009

Deletion of activating Fcgamma receptors does not confer protection in murine cryoglobulinemia-associated membranoproliferative glomerulonephritis.

Am J Pathol 2009 Jul 15;175(1):107-18. Epub 2009 Jun 15.

Department of Pathology, University of Washington, Seattle, WA 98195, USA.

Many types of glomerulonephritis are initiated by the deposition of immune complexes, which induce tissue injury via either engagement of Fc receptors on effector cells or via complement activation. Four murine Fcgamma receptors (FcgammaRs) have been identified at present. Ligand binding to FcgammaRI, III, and IV induces cell activation via the immunoreceptor tyrosine-based activation motif on the common gamma chain (FcRgamma). In this study, FcRgamma chain knockout (FcRgamma(-/-)) mice were crossed with thymic stromal lymphopoietin transgenic (TSLPtg) mice, which develop cryoglobulinemic membranoproliferative glomerulonephritis (MPGN). Female mice were studied at 30 and 50 days of age, when MPGN is in early and fully developed stages, respectively. Both TSLPtg and TSLPtg/FcRgamma(-/-) mice developed MPGN with massive glomerular immune deposits, mesangial cell proliferation, extensive mesangial matrix accumulation, and macrophage influx. TSLPtg/FcRgamma(-/-) mice had more glomerular immune complex deposits and higher levels of circulating cryoglobulins, IgG2a, IgG2b, and IgM, compared with TSLPtg mice. TSLPtg and TSLPtg/FcRgamma(-/-) mice developed similar levels of proteinuria. These results demonstrated that deletion of activating FcgammaRs does not confer protection in this model of immune complex-mediated MPGN. The findings contradict accepted paradigms on the role of activating FcgammaRs in promoting features of glomerulonephritis as seen in other model systems. We speculate engagement of FcgammaRs on cells such as monocytes/macrophages may be important for the clearance of deposited immune complexes and extracellular matrix proteins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2353/ajpath.2009.081159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2708799PMC
July 2009

Therapy outcome in peritoneal dialysis patients transferred from haemodialysis.

Nephrol Dial Transplant 2009 Sep 2;24(9):2889-94. Epub 2009 Apr 2.

Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdańsk, Poland.

Background: Haemodialysis (HD) and peritoneal dialysis (PD) should be regarded as complementary methods of renal replacement therapy. Approximately 10-20% of patients on PD are transferred annually to HD due to technique failure. Much smaller proportion of patients changes modality from HD to PD, predominantly due to vascular access problems, cardiac disease or patient preference. The effects of these transfers on therapy outcome, patient and technique survival have not been studied, with research focusing on outcome measures within the single modality and comparisons between the two methods.

Methods: We have analysed retrospectively a cohort of 264 patients treated with PD in a single PD centre during 1994-2006. Patient characteristics, therapy measures and outcome of patients were compared between patients for whom PD was the initial method of renal replacement therapy (group 1, n = 197) and those transferred to PD from haemodialysis because of complications (group 2, n = 67). The Kaplan-Meier method and Cox proportional hazards multiple regression analysis were used to assess patient and technique survival.

Results: In patients transferred from HD, significantly less had diabetes (11.9% versus 38.1%, P < 0.0001) and there were also significantly more females (57% versus 42.2%, P < 0.05). Baseline Kt/V was significantly higher in the primary PD therapy group (2.46 +/- 0.57 versus 2.11 +/- 0.48, P < 0.001), due to lower residual renal function in patients transferred from HD. Group 2 had also significantly higher peritonitis rate (0.86 versus 0.62 episode/year, P < 0.05). During the time of observation, 71 patients have died, in 100 patients kidney transplantation was performed, 56 were transferred to HD, renal function recovered in 5 and 32 were still on PD at the end of the study. No significant differences were observed in unadjusted patient survival, but technique survival was significantly lower in group 2 (P < 0.05). In the Cox multiple regression model, diabetes status, age and albumin level significantly influenced survival. Relative risk of death was not increased significantly in patients transferred from HD.

Conclusions: Our data suggest that outcome of patients transferred from HD is similar to that achieved in patients in whom PD is the first choice therapy. Thus, this option should be strongly considered in patients experiencing complications on HD, mainly vascular access problems, heart failure or intradialytic hypotension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfp132DOI Listing
September 2009

Imatinib suppresses cryoglobulinemia and secondary membranoproliferative glomerulonephritis.

J Am Soc Nephrol 2009 Jan 19;20(1):68-77. Epub 2008 Nov 19.

Department of Pathology, University of Washington, 1959 NE Pacific Avenue, Box 357470, Seattle, WA 98195, USA.

Imatinib is a receptor tyrosine kinase inhibitor that blocks the activity of c-Abl, c-Kit, and PDGF receptors. We tested the protective effects of imatinib in thymic stromal lymphopoietin transgenic mice, a model of cryoglobulinemia and associated membranoproliferative glomerulonephritis (MPGN), in which some glomerular manifestations likely result from PDGF receptor activation. Surprising, administration of imatinib beginning at weaning suppressed production of cryoglobulin, attenuating both the renal injury and systemic features of cryoglobulinemia. Flow cytometry suggested that inhibition of B cell development in the bone marrow likely caused the reduction in cryoglobulin production. In addition, administration of imatinib to thymic stromal lymphopoietin transgenic mice with established MPGN also diminished cryoglobulin production and reversed the renal and systemic lesions. These data suggest that treatment with imatinib may be a novel therapeutic approach for cryoglobulinemia and MPGN in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1681/ASN.2008010036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615727PMC
January 2009

Inducible rodent models of acquired podocyte diseases.

Am J Physiol Renal Physiol 2009 Feb 10;296(2):F213-29. Epub 2008 Sep 10.

Division of Nephrology, Department of Medicine, University of Washington School of Medicine, 1959 NE Pacific St., Box 356521, Seattle, WA 98195, USA.

Glomerular diseases remain the leading cause of chronic and end-stage kidney disease. Significant advances in our understanding of human glomerular diseases have been enabled by the development and better characterization of animal models. Diseases of the glomerular epithelial cells (podocytes) account for the majority of proteinuric diseases. Rodents have been extensively used experimentally to better define mechanisms of disease induction and progression, as well as to identify potential targets and therapies. The development of podocyte-specific genetically modified mice has energized the research field to better understand which animal models are appropriate to study acquired podocyte diseases. In this review we discuss inducible experimental models of acquired nondiabetic podocyte diseases in rodents, namely, passive Heymann nephritis, puromycin aminonucleoside nephrosis, adriamycin nephrosis, liopolysaccharide, crescentic glomerulonephritis, and protein overload nephropathy models. Details are given on the model backgrounds, how to induce each model, the interpretations of the data, and the benefits and shortcomings of each. Genetic rodent models of podocyte injury are excluded.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajprenal.90421.2008DOI Listing
February 2009

Higher levels of leflunomide are associated with hemolysis and are not superior to lower levels for BK virus clearance in renal transplant patients.

Clin J Am Soc Nephrol 2008 May 27;3(3):829-35. Epub 2008 Mar 27.

Department of Medicine, Division of Nephrology, University of Washington, Seattle, Washington 98195, USA.

Background And Objectives: Leflunomide use in renal transplantation has been increasing. Outcome correlation and safety data are still to be refined. The goals of this study were to report one center's experience with leflunomide, specifically the correlation of leflunomide levels with the outcomes of BK nephropathy and the observed toxic effects during the treatment with leflunomide.

Design, Setting, Participants, & Measurements: Leflunomide was used in 21 patients with BK nephropathy. These patients were divided into two groups on the basis of the leflunomide levels achieved: Low-level group (<40 microg/ml) and high-level group (>40 microg/ml).

Results: During 13 mo of follow-up, there was no difference in the rate of serum BK viral clearance between the groups. There were three graft losses in the low-level group and one in the high-level group; however, creatinine levels were higher at the time of starting leflunomide in the low-level group. Leflunomide was also used in six patients with chronic allograft injury. No graft loss was observed during the follow-up period of 16 mo. Treatment with leflunomide seemed to be associated with a new toxicity, hemolysis, seen in four of the 27 patients so treated. Patients with hemolysis had high leflunomide levels (81.4 +/- 14 microg/ml) and worsening allograft function. Two patients had histologic evidence of thrombotic microangiopathy, which led to graft loss in one patient.

Conclusions: The clinical correlation between leflunomide levels and outcomes needs to be further refined. This study described a possible association of leflunomide with thrombotic microangiopathy, especially at higher levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2215/CJN.03930907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386698PMC
May 2008

VEGF inhibition and renal thrombotic microangiopathy.

N Engl J Med 2008 Mar;358(11):1129-36

Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.

The glomerular microvasculature is particularly susceptible to injury in thrombotic microangiopathy, but the mechanisms by which this occurs are unclear. We report the cases of six patients who were treated with bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), in whom glomerular disease characteristic of thrombotic microangiopathy developed. To show that local reduction of VEGF within the kidney is sufficient to trigger the pathogenesis of thrombotic microangiopathy, we used conditional gene targeting to delete VEGF from renal podocytes in adult mice; this resulted in a profound thrombotic glomerular injury. These observations provide evidence that glomerular injury in patients who are treated with bevacizumab is probably due to direct targeting of VEGF by antiangiogenic therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa0707330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030578PMC
March 2008

Renin-angiotensin system blockade is renoprotective in immune complex-mediated glomerulonephritis.

J Am Soc Nephrol 2008 Jun 12;19(6):1168-76. Epub 2008 Mar 12.

Department of Pathology, University of Washington, 1959 NE Pacific Avenue, Seattle, WA 98195, USA.

Blockade of the renin-angiotensin system is renoprotective in a variety of chronic nephropathies, but the direct effect of such treatment in active, immune complex-mediated glomerulonephritis is unknown. This study investigated the short- and long-term effects of an angiotensin-converting enzyme inhibitor (enalapril) and an angiotensin II type 1 receptor blocker (losartan) in thymic stromal lymphopoietin transgenic (TSLPtg) mice, which develop mixed cryoglobulinemia and severe cryoglobulinemia-associated membranoproliferative glomerulonephritis. Enalapril and losartan each reduced hypertension, proteinuria, glomerular extracellular matrix deposition, and mesangial cell activation in TSLPtg mice. These renoprotective effects were not observed with hydralazine treatment, despite a similar antihypertensive effect. Treatment with enalapril or losartan also decreased renal plasminogen activator inhibitor-1 in TSLPtg mice, assessed by immunohistochemistry and quantitative real-time reverse transcriptase-PCR. None of the treatments affected immune complex deposition or macrophage infiltration. Overall, enalapril- and losartan-treated TSLPtg mice survived significantly longer than untreated TSLPtg mice. These studies demonstrate that angiotensin blockade may provide renoprotective benefits, independent of its BP-lowering effect, in the treatment of active immune complex-mediated glomerulonephritis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1681/ASN.2007050607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2396930PMC
June 2008

Protease nexin-1, tPA, and PAI-1 are upregulated in cryoglobulinemic membranoproliferative glomerulonephritis.

J Am Soc Nephrol 2008 Feb 16;19(2):243-51. Epub 2008 Jan 16.

Department of Pathology, Division of Nephrology, University of Washington, Seattle, Washington 98195, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1681/ASN.2007030367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2396743PMC
February 2008

Identification of platelet-derived growth factor D in human chronic allograft nephropathy.

Hum Pathol 2008 Mar 9;39(3):393-402. Epub 2008 Jan 9.

Institute of Nephrology, Peking University, First Hospital, 100034 Beijing, China.

Chronic allograft nephropathy (CAN), a descriptive term denoting chronic scarring injury of the renal parenchyma and vasculature in allograft kidneys arising from various etiologies including chronic rejection, is the most common cause of late allograft failure, but mediators of this progressive injury largely remain unknown. We hypothesized that platelet-derived growth factor D (PDGF-D) and its specific receptor PDGF-Rbeta may be an important mediator in the pathogenesis of CAN and, hence, sought to identify its expression in this setting. Allograft nephrectomies demonstrating CAN, obtained from patients with irreversible transplant kidney failure (n = 15), were compared with renal tissues without prominent histopathological abnormalities (n = 18) and a series of renal allograft biopsies demonstrating acute vascular rejection (AVR) (n = 12). Antibodies to PDGF-D and PDGF-Rbeta were used for immunohistochemistry. Double and triple immunohistochemistry was used to identify cell types expressing PDGF-D. PDGF-D was widely expressed in most neointimas in arteries exhibiting the chronic arteriopathy of CAN and only weakly expressed in a small proportion of sclerotic arteries in the other 2 groups. Double and triple immunolabeling demonstrated that the neointimal cells expressing PDGF-D were alpha-smooth muscle actin-expressing cells, but not infiltrating macrophages or endothelial cells. PDGF-Rbeta expression evaluated in serial sections was localized to the same sites where neointimal PDGF-D was expressed. PDGF-Rbeta was expressed in interstitial cells more abundantly in the CAN group compared with the normal and AVR groups, without demonstrable colocalization of PDGF-D. PDGF-D is present in the neointima of the arteriopathy of CAN, where it can engage PDGF-Rbeta to promote mesenchymal cell migration, proliferation, and neointima formation. PDGF-D may engage the PDGF-Rbeta to promote interstitial injury in chronic allograft injury, but its sources within the interstitium were unidentified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.humpath.2007.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2703673PMC
March 2008