Publications (25)132.79 Total impact
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Article: The diagnosis and characteristics of renal heavy-chain and heavy/light-chain amyloidosis and their comparison with renal light-chain amyloidosis.
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ABSTRACT: Little is known about the rare entities of heavy- and light-chain amyloidosis (AHL) and heavy-chain amyloidosis (AH). Here, we report the renal and hematological characteristics, pathology, and outcome of 16 patients with renal AH/AHL (5 with AH and 11 with AHL) and compare them with 202 patients with renal light-chain amyloidosis (AL) diagnosed during the same time period. All cases were diagnosed by kidney biopsy that showed Congo red-positive deposits. Amyloid typing was done by laser microdissection and mass spectrometry (LMD/MS) on 12 patients or by immunofluorescence on four patients. All patients with renal AH/AHL were Caucasians, with a male/female ratio of 2.2 and a median age at biopsy of 63 years. Compared with patients with renal AL, those with renal AH/AHL had less frequent concurrent cardiac involvement, higher likelihood of having circulating complete monoclonal immunoglobulin, lower sensitivity of fat pad biopsy and bone marrow biopsy for detecting amyloid, higher incidence of hematuria, and better patient survival. The hematological response to chemotherapy was comparable with renal AL. In 42% of patients, AH/AHL could not have been diagnosed without LMD/MS. Thus, renal AH/AHL is an uncommon and underrecognized form of amyloidosis, and its diagnosis is greatly enhanced by the use of LMD/MS for amyloid typing. The accurate histological diagnosis of renal AH/AHL and distinction from AL may have important clinical and prognostic implications.Kidney International advance online publication, 9 January 2013; doi:10.1038/ki.2012.414.Kidney International 01/2013; · 6.61 Impact Factor -
Article: Membranous glomerulonephritis is a manifestation of IgG4-related disease.
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ABSTRACT: IgG4-related disease (IgG4-RD) is a systemic immune-mediated disease that typically manifests as fibro-inflammatory masses that can affect nearly any organ system. Renal involvement by IgG4-RD usually takes the form of IgG4-related tubulointerstitial nephritis, but cases of membranous glomerulonephritis (MGN) have also been described. Here we present a series of 9 patients (mean age at diagnosis 58 years) with MGN associated with IgG4-RD. All patients showed MGN on biopsy, presented with proteinuria (mean 8.3 g/day), and most had elevated serum creatinine (mean 2.2 mg/dl). Seven patients had known extrarenal involvement by IgG4-RD, with 5 patients having concurrent IgG4-related tubulointerstitial nephritis. Immunohistochemical analysis for the phospholipase A2 receptor, a marker of primary MGN, was negative in all 8 biopsies so examined. Six of 7 patients with available follow-up (mean 39 months) were treated with immunosuppressive agents; one untreated patient developed end-stage renal disease and underwent transplantation, without recurrence at 12 years after transplant. All 6 treated patients showed decreased proteinuria (mean 1.2 g/day), and most showed decreased serum creatinine (mean 1.4 mg/dl). Thus, MGN should be included in the spectrum of IgG4-RD and should be suspected in proteinuric IgG4-RD patients. Conversely, patients with MGN and an appropriate clinical history should be evaluated for IgG4-RD.Kidney International advance online publication, 19 December 2012; doi:10.1038/ki.2012.382.Kidney International 12/2012; · 6.61 Impact Factor -
Article: Immunotactoid glomerulopathy: clinicopathologic and proteomic study.
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ABSTRACT: Background Immunotactoid glomerulopathy (ITG) is a rare glomerular disease. Here, we report the largest clinicopathologic series of ITG and define its proteomic profile.Methods The characteristics of 16 ITG patients who were identified from our pathology archives are provided between 1993 and 2011. We also performed laser microdissection and mass spectrometry (LMD/MS) in three cases.ResultsPresentation included proteinuria (100%), nephrotic syndrome (69%), renal insufficiency (50%) and microhematuria (80%). Hypocomplementemia was present in 46% and a serum M-spike in 63%. Hematologic malignancy was present in 38%, including chronic lymphocytic leukemia in 19%, lymphoplasmacytic lymphoma in 13% and myeloma in 13%. The pattern of glomerular injury was membranoproliferative (56%), membranous (31%) or proliferative (13%) glomerulonephritis. The microtubular deposits were immunoglobulin light chain restricted in 69% and had a mean diameter of 31 nm (range 17-52). During an average of 48 months of follow-up for 12 patients, 50% had remission, 33% had persistent renal dysfunction and 17% progressed to end-stage renal disease. Proteomic analysis by LMD/MS revealed the presence of immunoglobulins, monotypic light chains, complement factors of the classical and terminal pathway and small amount of serum amyloid P-component.Conclusions Hematologic malignancy, particularly lymphoma, is not uncommon in ITG. ITG appears to have a better prognosis than other paraprotein-related renal lesions, with a half of patients expected to recover kidney function with immunosuppressive therapy or chemotherapy. The proteomic profile of ITG is consistent with deposition of monotypic immunoglobulins and activation of the classical and terminal pathway of complement.Nephrology Dialysis Transplantation 08/2012; · 3.40 Impact Factor -
Article: Laser microdissection and mass spectrometry-based proteomics aids the diagnosis and typing of renal amyloidosis.
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ABSTRACT: Accurate diagnosis and typing of renal amyloidosis is critical for prognosis, genetic counseling, and treatment. Laser microdissection and mass spectrometry are emerging techniques for the analysis and diagnosis of many renal diseases. Here we present the results of laser microdissection and mass spectrometry performed on 127 cases of renal amyloidosis during 2008-2010. We found the following proteins in the amyloid deposits: immunoglobulin light and heavy chains, secondary reactive serum amyloid A protein, leukocyte cell-derived chemotaxin-2, fibrinogen-α chain, transthyretin, apolipoprotein A-I and A-IV, gelsolin, and β-2 microglobulin. Thus, laser microdissection of affected areas within the kidney followed by mass spectrometry provides a direct test of the composition of the deposit and forms a useful ancillary technique for the accurate diagnosis and typing of renal amyloidosis in a single procedure.Kidney International 04/2012; 82(2):226-34. · 6.61 Impact Factor -
Article: Clinicopathologic correlations in multiple myeloma: a case series of 190 patients with kidney biopsies.
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ABSTRACT: Renal involvement is common in multiple myeloma. In this study, we examined kidney biopsy findings in patients with multiple myeloma and correlated them with their clinical renal and hematologic characteristics. Case series. 190 Mayo Clinic patients with multiple myeloma who underwent kidney biopsy between 1997-2011 were identified from our kidney biopsy database. Patients had an established diagnosis of multiple myeloma or multiple myeloma was diagnosed shortly after the results of kidney biopsy, which prompted bone marrow biopsy. Myeloma cast nephropathy (MCN), AL amyloidosis, and monoclonal immunoglobulin deposition disease (MIDD). Renal morphologic changes, clinical renal and hematologic characteristics at kidney biopsy, renal and patient outcomes. Paraprotein-associated lesions were seen in 73% of patients; non-paraprotein-associated lesions, in 25%; and no pathology, in 2%. The most common paraprotein-associated lesions were MCN (33%), MIDD (22%), and amyloidosis (21%). The most common non-paraprotein-associated lesions were acute tubular necrosis (9%), hypertensive arteriosclerosis (6%), and diabetic nephropathy (5%). Patients with MIDD were younger than those with MCN or amyloidosis. Urine paraprotein size and bone marrow plasma cell percentage were higher in MCN than amyloidosis or MIDD. Nephrotic syndrome was more common in amyloidosis than MIDD. Percentage of albuminuria was highest in amyloidosis and lowest in MCN. Median kidney survival from kidney biopsy was 20, 30, and 51 months for MCN, amyloidosis, and MIDD, respectively (P = 0.2). Median patient survival from multiple myeloma diagnosis was 44, 58, and 62 months for MCN, amyloidosis, and MIDD, respectively (P = 0.4). Retrospective nature. The spectrum of renal lesions in multiple myeloma is more heterogeneous than previously reported. Clinical features favoring amyloidosis over MIDD include older age, absence of kidney failure, presence of nephrotic syndrome, absence of hematuria, and >50% albuminuria.American Journal of Kidney Diseases 03/2012; 59(6):786-94. · 5.43 Impact Factor -
Article: Renal monoclonal immunoglobulin deposition disease: a report of 64 patients from a single institution.
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ABSTRACT: To better define the clinical-pathologic spectrum and prognosis of monoclonal immunoglobulin deposition disease (MIDD), this study reports the largest series. Characteristics of 64 MIDD patients who were seen at Mayo Clinic are provided. Of 64 patients with MIDD, 51 had light chain deposition disease, 7 had heavy chain deposition disease, and 6 had light and heavy chain deposition disease. The mean age at diagnosis was 56 years, and 23 patients (36%) were ≤50 years of age. Clinical evidence of dysproteinemia was present in 62 patients (97%), including multiple myeloma in 38 (59%). M-spike was detected on serum protein electrophoresis in 47 (73%). Serum free light chain ratio was abnormal in all 51 patients tested. Presentation included renal insufficiency, proteinuria, hematuria, and hypertension. Nodular mesangial sclerosis was seen in 39 patients (61%). During a median of 25 months of follow-up (range, 1-140) in 56 patients, 32 (57%) had stable/improved renal function, 2 (4%) had worsening renal function, and 22 (39%) progressed to ESRD. The mean renal and patient survivals were 64 and 90 months, respectively. The disease recurred in three of four patients who received a kidney transplant. Patients with MIDD generally present at a younger age than those with light chain amyloidosis or light chain cast nephropathy. Serum free light chain ratio is abnormal in all MIDD patients, whereas only three-quarters have abnormal serum protein electrophoresis. The prognosis for MIDD is improving compared with historical controls, likely reflecting earlier detection and improved therapies.Clinical Journal of the American Society of Nephrology 12/2011; 7(2):231-9. · 5.23 Impact Factor -
Article: Clinical features of patients with immunoglobulin light chain amyloidosis (AL) with vascular-limited deposition in the kidney.
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ABSTRACT: In the kidney, immunoglobulin light chain amyloidosis (AL) can be deposited in vascular-limited AL (V-AL) or diffuse (D-AL) pattern. These patterns are associated with different clinical presentations. A nested case study was performed to describe these differences. V-AL was defined by the vascular-limited deposits. Cases were matched for age, sex and date of renal biopsy. There were 12 cases of V-AL (mean age 61 ± 11 years) and 24 cases of D-AL. Median follow-up was 26 months for V-AL and 38 months for D-AL, P = 0.14. Lambda was more common in D-AL (83.3%) than V-AL (50%, P = 0.04). Cardiac function was similar between the two groups. V-AL patients presented with lower renal function (serum creatinine = 2.1 versus 1.3 mg/dL, P = 0.02; estimated glomerular filtration rate 31 versus 59 mL/min/1.73m(2), P = 0.01 and creatinine clearance 38.5 versus 64 mL/min/1.73m(2), P = 0.02, respectively). Proteinuria was low grade in V-AL [0.4 (0.09-0.98) g/day] compared to nephrotic range in D-AL patients [8.0 (0.2-22) g/day, P < 0.001]. Stem cell transplantation was performed on 62.5% of the D-AL but on only 25% of the V-AL, P = 0.08. Median survival was longer in patients with D-AL (77.2 months) versus V-AL (40.6 months, log-rank P = 0.02). Our study found that V-AL patients presented with more severe renal insufficiency and less proteinuria than D-AL. There was a preference for λ light chain in the D-AL that was not noted in the V-AL. Patients with D-AL in this study had a longer median survival but most of them were stem cell transplantation candidates.Nephrology Dialysis Transplantation 11/2011; 27(3):1097-101. · 3.40 Impact Factor -
Article: Acquired glomerular lesions in patients with Down syndrome.
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ABSTRACT: The long-term survival of persons with Down syndrome has dramatically increased over the past 50 years. There are no studies addressing the spectrum of glomerular lesions in these patients. We reviewed the clinical-pathologic characteristics of 17 patients with Down syndrome who underwent renal biopsy. The cohort consisted of 12 whites and 5 African Americans with mean age of 29 years (range, 6-45 years). History of hypothyroidism was present in 8 patients. Renal presentations included renal insufficiency (15 patients, mean serum creatinine 3.4 mg/dL), proteinuria (all patients, including 3 with nephrotic syndrome, mean 24-hour urine protein 4.2 g), and hematuria (14 patients, including 4 with gross hematuria). The glomerular diseases found on biopsy were IgA nephropathy (n = 5 patients), focal segmental glomerulosclerosis (n = 4), membranoproliferative glomerulonephritis (n = 2), acute postinfectious glomerulonephritis (n = 2), pauci-immune crescentic glomerulonephritis (n = 2), membranous glomerulonephritis (n = 1), and lupus nephritis (n = 1). Follow-up (mean, 47 months; range, 2-141 months) was available on 16 patients (94%). Two patients (1 with membranous glomerulonephritis and 1 with acute postinfectious glomerulonephritis) had complete remission; 8 patients (4 with IgA nephropathy, 2 with focal segmental glomerulosclerosis, 1 with lupus nephritis, and 1 with acute postinfectious glomerulonephritis) had chronic kidney disease; and 6 patients (2 with pauci-immune crescentic glomerulonephritis, 2 with membranoproliferative glomerulonephritis, 1 with IgA nephropathy, and 1 with focal segmental glomerulosclerosis) progressed to end-stage renal disease, 4 of whom died. In summary, a wide spectrum of glomerular diseases can be seen in patients with Down syndrome, with IgA nephropathy and focal segmental glomerulosclerosis being the most common. Renal biopsy is necessary to determine the type of glomerular lesion and appropriate treatment.Human pathology 07/2011; 43(1):81-8. · 3.03 Impact Factor -
Article: Diagnosis of IgG4-related tubulointerstitial nephritis.
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ABSTRACT: IgG4-related systemic disease is an autoimmune disease that was first recognized in the pancreas but also affects other organs. This disease may manifest as tubulointerstitial nephritis (IgG4-TIN), but its clinicopathologic features in the kidney are not well described. Of the 35 patients with IgG4-TIN whose renal tissue specimens we examined, 27 (77%) had acute or progressive chronic renal failure, 29 (83%) had involvement of other organ systems, and 18 of 23 (78%) had radiographic abnormalities. Elevated total IgG or IgG4 serum levels were present in 79%. All pathologic specimens featured plasma cell-rich TIN, with most showing diffuse, expansile interstitial fibrosis. Immune complexes along the tubular basement membranes were present in 25 of 30 (83%). All specimens had a moderate to marked increase in IgG4+ plasma cells by immunohistochemistry. We used a control group of 175 pathologic specimens with plasma cell-rich interstitial infiltrates that can mimic IgG4-TIN to examine the diagnostic utility of IgG4 immunostaining. Excluding pauci-immune necrotizing and crescentic glomerulonephritis, IgG4 immunohistochemistry had a sensitivity of 100% (95% CI 90-100%) and a specificity of 92% (95% CI 86-95%) for IgG4-TIN. Of the 19 patients with renal failure for whom treatment and follow-up data were available, 17 (89%) responded to prednisone. In summary, because no single test definitively diagnoses IgG4-related systemic disease, we rely on a combination of histologic, immunophenotypic, clinical, radiographic, and laboratory features. When the disease manifests in the kidney, our data support diagnostic criteria that can distinguish IgG4-TIN from other types of TIN.Journal of the American Society of Nephrology 06/2011; 22(7):1343-52. · 9.66 Impact Factor -
Article: Myeloproliferative neoplasms cause glomerulopathy.
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ABSTRACT: Myeloproliferative neoplasms are clonal hematopoietic stem cell disorders that can produce an undefined glomerulopathy. To better characterize the glomerular disease associated with myeloproliferative neoplasms, we evaluated features of 11 patients with myeloproliferative neoplasm-related glomerulopathy that included 8 patients with primary myelofibrosis, and 1 each with chronic myelogenous leukemia, polycythemia vera, and essential thrombocythemia. Indications for biopsy were nephrotic-range proteinuria (nephrotic syndrome in four) and chronic renal insufficiency. The mean time from diagnosis of the neoplasms to biopsy was 7.2 years. Histologically, mesangial sclerosis and hypercellularity were seen in all 11 cases, segmental sclerosis in 8, features of chronic thrombotic microangiopathy in 9, and intracapillary hematopoietic cells in 4. On follow-up, seven patients had persistent renal dysfunction and four progressed to end-stage renal disease (ESRD). Thus, glomerulopathy appears to be a late complication of myeloproliferative neoplasms, particularly primary myelofibrosis, with guarded prognosis. Greater awareness of this entity and larger studies are needed to define possible therapies.Kidney International 06/2011; 80(7):753-9. · 6.61 Impact Factor -
Article: Fibrillary glomerulonephritis: a report of 66 cases from a single institution.
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ABSTRACT: Fibrillary glomerulonephritis (FGN) is a rare primary glomerular disease. Most previously reported cases were idiopathic. To better define the clinical-pathologic spectrum and prognosis, we report the largest single-center series with the longest follow-up. The characteristics of 66 FGN patients who were seen at Mayo Clinic, Rochester, between 1993 and 2010 are provided. The mean age at diagnosis was 53 years. Ninety-five percent of patients were white, and the female:male ratio was 1.2:1. Underlying malignancy (most commonly carcinoma), dysproteinemia, or autoimmune disease (most commonly Crohn's disease, SLE, Graves' disease, and idiopathic thrombocytopenic purpura), were present in 23, 17, and 15% of patients, respectively. Presentation included proteinuria (100%), nephrotic syndrome (38%), renal insufficiency (66%), hematuria (52%), and hypertension (71%). The most common histologic pattern was mesangial proliferative/sclerosing GN followed by membranoproliferative GN. During an average of 52.3 months of follow-up for 61 patients with available data, 13% had complete or partial remission, 43% had persistent renal dysfunction, and 44% progressed to ESRD. The disease recurred in 36% of 14 patients who received a kidney transplant. Independent predictors of ESRD by multivariate analysis were older age, higher creatinine and proteinuria at biopsy, and higher percentage of global glomerulosclerosis. Underlying malignancy, dysproteinemia, or autoimmune diseases are not uncommon in patients with FGN. Prognosis is poor, although remission may occur in a minority of patients without immunosuppressive therapy. Age, degree of renal impairment at diagnosis, and degree of glomerular scarring are predictors of renal survival.Clinical Journal of the American Society of Nephrology 03/2011; 6(4):775-84. · 5.23 Impact Factor -
Article: Postinfectious glomerulonephritis in the elderly.
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ABSTRACT: Postinfectious glomerulonephritis (PIGN) is primarily a childhood disease that occurs after an upper respiratory tract infection or impetigo; its occurrence in older patients is not well characterized. Here, we report 109 cases of PIGN in patients ≥65 years old diagnosed by renal biopsy. The male to female ratio was 2.8:1. An immunocompromised background was present in 61%, most commonly diabetes or malignancy. The most common site of infection was skin, followed by pneumonia and urinary tract infection. The most common causative agent was staphylococcus (46%) followed by streptococcus (16%) and unusual gram-negative organisms. Hypocomplementemia was present in 72%. The mean peak serum creatinine was 5.1 mg/dl, and 46% of patients required acute dialysis. The most common light microscopic patterns were diffuse (53%), focal (28%), and mesangial (13%) proliferative glomerulonephritis. IgA-dominant PIGN occurred in 17%. Of the 72 patients with ≥3 months of follow-up (mean, 29 months), 22% achieved complete recovery, 44% had persistent renal dysfunction, and 33% progressed to ESRD. The presence of diabetes, higher creatinine at biopsy, dialysis at presentation, the presence of diabetic glomerulosclerosis, and greater tubular atrophy and interstitial fibrosis predicted ESRD. In summary, the epidemiology of PIGN is shifting as the population ages. Older men and patients with diabetes or malignancy are particularly at risk, and the sites of infection and causative organisms differ from the typical childhood disease. Prognosis for these older patients is poor, with fewer than 25% recovering full renal function.Journal of the American Society of Nephrology 11/2010; 22(1):187-95. · 9.66 Impact Factor -
Article: Proliferative glomerulonephritis with monoclonal IgG deposits recurs in the allograft.
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ABSTRACT: Proliferative GN with monoclonal IgG deposits (PGNMID) is a newly described entity resembling immune complex GN. Its potential to recur in the allograft is undefined. The first cases of recurrent PGNMID in the allograft are reported. The cohort includes four Caucasians (3 women, 1 man) with a mean age 58.5 years. No patient had M spike or hematologic malignancy. Recurrence was first documented by biopsy at a mean of 3.8 months posttransplant for indications of renal insufficiency in four patients, proteinuria in three patients, and microhematuria in three patients. Monoclonal IgG deposits (3 IgG3κ and 1 IgG3λ) in the transplants had identical heavy- and light-chain isotypes as in the native kidneys. In two patients, a pattern of endocapillary GN was identified in the native and transplant biopsies, whereas two patients with membranoproliferative GN in the native kidney developed endocapillary or mesangial GN in the transplant. Recurrence was treated with combined high-dose prednisone plus rituximab (n = 3) or plus cyclophosphamide (n = 1). After a mean posttransplant follow-up of 43 months, all four patients achieved reduction in proteinuria and three had reduction in creatinine. Repeat biopsies showed reduced histologic activity after treatment. PGNMID can recur in the transplant despite the absence of a serum M spike. Recurrence is heralded by proteinuria, hematuria, and allograft dysfunction and manifests diverse histologic patterns. Although the pathogenesis remains unknown, early immunosuppressive therapy appears to stabilize the course.Clinical Journal of the American Society of Nephrology 09/2010; 6(1):122-32. · 5.23 Impact Factor -
Article: Mass spectrometry-based proteomic diagnosis of renal immunoglobulin heavy chain amyloidosis.
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ABSTRACT: Amyloidosis is a group of disorders characterized by accumulation of extracellular deposition of proteins as insoluble aggregates. The clinical management of amyloidosis is based on identifying the underlying etiology and accurate typing of the amyloid. Ig heavy chain amyloid involving the kidney is poorly recognized and often poses a diagnostic dilemma. DESIGN, SETTING, PARTICIPANTS, & MEASURES: In this study, we describe the use of laser microdissection (LMD) and mass spectrometry (MS)-based proteomic analysis for the accurate typing of 14 cases of amyloidosis. We also describe the clinicopathologic findings of four problematic cases of renal Ig heavy chain amyloidosis that required LMD/MS proteomic analysis for accurate typing of the amyloid. LMD/MS proteomic data of four cases of Ig heavy chain renal amyloidosis showed Ig heavy chains with or without light chains. The break up of the Ig heavy chains was as follows: one case showed Igγ1 chain constant region and λ light chains, one case showed Igα chain constant region and κ light chains variable and constant regions, whereas two cases showed Igγ3 chain constant region and heavy chains variable region I and/or III without light chains. We compare the LMD/MS proteomic data of Ig heavy chain renal amyloid with that of other types of amyloid, including Ig light chains, serum amyloid A, fibrinogen A-α chain renal amyloid, and transthyretin amyloid. We conclude that LMD/MS is a sensitive and specific tool for diagnosis and accurate typing of renal amyloidosis, including Ig heavy chain amyloid.Clinical Journal of the American Society of Nephrology 09/2010; 5(12):2180-7. · 5.23 Impact Factor -
Article: C1q deposition in the renal allograft: a report of 24 cases.
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ABSTRACT: C1q nephropathy is an uncommon glomerular disease characterized by dominant or codominant mesangial staining for C1q in the absence of systemic lupus erythematosus. There are no series in the literature addressing the significance of C1q deposition in the renal allograft. We retrospectively analyzed 24 patients, most of whom were white (83%) and male (63%), with a mean age at transplant of 31 years. None of the patients were diagnosed with C1q nephropathy in the native kidney or had any features of systemic lupus erythematosus. The mean time from transplant to detection of mesangial C1q deposits was 37 months (>12 months in 71% of cases). Half of the patients had a preceding infection. The indication for biopsy was surveillance (63%) or graft dysfunction (37%). At biopsy, 52% had proteinuria (>1g/day in only 17%). The mean creatinine was 1.8 mg per 100 ml. Only 9% developed hematuria and none had hypoalbuminemia. The glomerular pattern on light microscopy was mesangial hypercellularity (46%), focal segmental glomerulosclerosis (21%), or no lesions (33%). All cases showed intense (>or=2+) dominant (67%) or codominant (33%) mesangial staining for C1q on immunofluorescence. Mesangial electron-dense deposits were seen in 82% of cases. On follow-up (mean 1 year) of the 10 patients without rejection, most had stable creatinine with no or stable proteinuria, and none lost their graft. We conclude that C1q-dominant mesangial deposition in the renal allograft is a morphological pattern with no apparent clinical significance in the majority of patients. It is usually detected after the first year. The rate of preceding infection and the prevalence of proteinuria seem to be similar to the renal transplant recipients in general. Most cases show mesangial hypercellularity or no glomerular changes on light microscopy.Modern Pathology 08/2010; 23(8):1080-8. · 4.79 Impact Factor -
Article: Crystalline nephropathy due to 2,8-dihydroxyadeninuria: an under-recognized cause of irreversible renal failure.
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ABSTRACT: 2,8-dihydroxyadeninuria (DHA) disease (also called 2,8 dihydroxyadeninuria) is a rare autosomal recessive disorder caused by complete adenine phosphoribosyltransferase deficiency and typically manifests as recurrent nephrolithiasis. Only rare cases of DHA nephrolithiasis have been reported from the USA. Herein, we report three American patients who developed DHA crystalline nephropathy leading to end-stage renal disease (ESRD) with recurrence in the allograft. Three cases of DHA crystalline nephropathy were identified from the Renal Pathology Laboratory of Mayo Clinic. Detailed clinical and pathologic descriptions are provided. All three patients were Caucasian adults with no history of obstructive nephropathy. Two patients had no history of nephrolithiasis and one had a single episode of stones 36 years prior to presentation. All patients presented with severe renal failure with a mean serum creatinine of 7.5 mg/dl. Renal biopsies revealed numerous tubular and interstitial brown DHA crystals, tubular degenerative changes and moderate to marked tubulointerstitial scarring. Two patients were initially misdiagnosed, one as primary hyperoxaluria and the other as chronic interstitial nephritis. All three patients progressed to ESRD, within 1 month following renal biopsy in two and after 9 months in one. All three patients underwent renal transplantation with early disease recurrence in three allografts in two patients. DHA disease is an under-recognized condition that can lead to irreversible renal failure and frequently recurs in the transplant. It should be included in the differential diagnosis of crystalline nephropathy, even in the absence of history of nephrolithiasis.Nephrology Dialysis Transplantation 06/2010; 25(6):1909-15. · 3.40 Impact Factor -
Article: Acute renal failure secondary to severe type I cryoglobulinemia following rituximab therapy for Waldenström's macroglobulinemia.
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ABSTRACT: Waldenström's macroglobulinemia is rare lymphoproliferative disorder characterized by the presence of a monoclonal IgM paraproteinemia. Cryoglobulinemia is a common sequela of Waldenström's macroglobulinemia present in 8-18% of the patients. Cryoglobulinemia has also been described as occurring after treatment with rituximab. In the previous report, the cryoglobulinemia was a transient phenomenon and did not carry any adverse effect. We present a case of an 80-year-old male with Waldenström's macroglobulinemia in whom the rituximab-induced cryoglobulinemia resulted in acute renal failure and a vasculitic rash. Cryoglobulins level reached a peak of 63%. The patient was successfully treated with plasmapheresis, chlorambucil and prednisone, with near-complete recovery of renal function. As this case illustrates, the rituximab-induced cryoglobulin is not always benign. Pre- and post-treatment monitoring of the cryoglobulin level is advised in these patients.Clinical and Experimental Nephrology 09/2008; 12(4):292-5. · 1.37 Impact Factor -
Article: A Comparison of splenectomy versus intensive posttransplant antidonor blood group antibody monitoring without splenectomy in ABO-incompatible kidney transplantation.
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ABSTRACT: Although most protocols for ABO-incompatible kidney transplantation have employed splenectomy, its utility is unproven. The aim of the current study was to compare the outcomes of ABO-incompatible living donor kidney transplantation with splenectomy versus a protocol involving intensive posttransplant antibody monitoring to maintain low levels of antiblood group antibody. We retrospectively studied all ABO-incompatible living donor kidney transplants at our institution between September 1999 and November 2004 (n=34). Prior to May 2003, all patients were included in a protocol involving pretransplant plasmapheresis and splenectomy at the time of transplant (n=23). After May 2003, splenectomy was not performed and a protocol that involved pretransplant anti-CD20 antibody and a more intensive posttransplant plasmapheresis regiment aimed at maintaining low levels of antiblood group antibody during the first 2 weeks following transplantation was utilized (n=11). Patient and graft survival was similar in the two groups. Humoral rejection occurred in 18% nonsplenectomized and 30% of splenectomized patients (P=0.68). Humoral rejection correlated with the baseline antibody titer in both groups. Individuals with elevated baseline antibody titer (> or =1:256) appear to be at high risk for humoral rejection regardless of protocol used. Antiblood group antibody levels 3 and 12 months after transplantation were similar in both groups. Splenectomy is not essential for successful ABO-incompatible kidney transplantation, although individuals with high baseline antidonor blood group antibody titers are at high risk for humoral rejection. The use of intensive posttransplant monitoring may help prevent antibody-mediated graft damage.Transplantation 01/2006; 80(11):1572-7. · 4.00 Impact Factor -
Article: Histologic findings of antibody-mediated rejection in ABO blood-group-incompatible living-donor kidney transplantation.
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ABSTRACT: The purpose of this study was to characterize the histology of antibody-mediated rejection (AMR) in ABO blood-group-incompatible (ABOI) kidney transplants as well as on protocol biopsies performed at the time of stable allograft function. Between 5/99 and 1/02, we performed 32 ABOI kidney transplants (13 A2, 19 non-A2 blood-group living donors). Nineteen biopsies were performed for allograft dysfunction, and 127 protocol biopsies were performed 0, 3, 7, 14, 28 days and 3 and 12 months post transplant. Twenty-five of 32 patients have functioning allografts (mean 585 days post transplant). Nine of 32 (28%) developed clinical AMR. Biopsy revealed glomerular thrombi (78%), mesangiolysis (78%), peritubular capillary C4d staining (56%) and neutrophil infiltration (67%), interstitial hemorrhage and necrosis (56%) and arteriolar thrombi (33%). Subclinical AMR was diagnosed by protocol biopsies in four patients. Findings consisted of glomerular thrombi (100%), mesangiolysis (25%), and C4d staining (100%). In late protocol biopsies performed 214-420 days post transplant, mild mesangiolysis was seen in 2/17 (11.7%), and C4d immunostaining was detected in 3/12 (25%). AMR is characterized by glomerular thrombi, mesangiolysis, peritubular capillary neutrophil infiltration interstitial hemorrhage, necrosis, and C4d deposition. Glomerular thrombi appear early in AMR and may appear prior to graft dysfunction.American Journal of Transplantation 02/2004; 4(1):101-7. · 6.39 Impact Factor -
Article: Influence of surveillance renal allograft biopsy on diagnosis and prognosis of polyomavirus-associated nephropathy.
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ABSTRACT: Polyomavirus-associated nephropathy (PVAN) is an increasingly prevalent cause of allograft dysfunction. In 18 histologically proven cases of PVAN managed by reduced immunosuppression, monitoring of serum creatinine, and repeated biopsy, graft outcomes were correlated with clinical and histologic indices. Six months postdiagnosis the status of each graft was classified as poor (N = 7) or satisfactory (N = 11). Poor transplant status was defined as graft loss, increased severity of PVAN on repeat biopsy, or serum creatinine>3.0 mg/dL. Diagnosis resulted from either surveillance allograft biopsies (N = 8) or biopsies performed for increased serum creatinine (nonsurveillance, N = 10). The surveillance biopsy group was more likely than the nonsurveillance group to have satisfactory graft status at 6 months (eight of eight vs. three of ten, P = 0.004) and had significantly lower serum creatinine at diagnosis, 3, and 6 months. Histologic scoring for chronic interstitial and tubular injury was lower in diagnostic surveillance biopsies compared to nonsurveillance biopsies (P = 0.01). Satisfactory transplant status was also associated with reduced or absent virus on repeat biopsy (P = 0.01). Poor transplant status was associated with a higher frequency of recipientneg/donorpos cytomegalovirus (CMV) serology (71% vs. 9%, P = 0.01). Surveillance allograft biopsy provides an important means for earlier detection of PVAN and permits timely alterations to immunosuppression. Early diagnosis is associated with a lesser degree of interstitial fibrosis at diagnosis and lower baseline and subsequent serum creatinine.Kidney International 08/2003; 64(2):665-73. · 6.61 Impact Factor
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Institutions
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2006–2012
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Mayo Foundation for Medical Education and Research
- Division of Nephrology and Hypertension
Rochester, MI, USA
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2002–2011
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Mayo Clinic - Rochester
- Transplant Center
Rochester, MN, USA
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