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M M Schwartz

Publications and source records attributed to M M Schwartz.

At least 19 recordsLinked to original sources
PubMed2006

Association of glomerular podocytopathy and nephrotic proteinuria in mesangial lupus nephritis.

We investigated a series of patients with systemic lupus erythematosus (SLE), who had sparse subepithelial and mesangial immune deposits. Our goal was to determine structure: function correlation. We examined whether proteinuria correlated with either capillary wall immune aggregate formation or abnormal podocyte morphology. Renal biopsies from patients with sparse (two or fewer subepithelial or intramembranous electron dense deposits per glomerular capillary loop) immune deposits and podocyte effacement were studied. Patients fulfilled criteria for the diagnosis of SLE. Cases were excluded if the biopsy showed endocapillary proliferation or necrosis. Eighteen biopsies were studied, five from patients with nephrotic range proteinuria (> or =3 g/day) and 13 from patients with non-nephrotic proteinuria (<3 g/day). The five nephrotic patients had a mean foot process effacement of 48% +/- 39% (range 10-100%). Thirteen non-nephrotic patients had a mean foot process effacement of 11.7% +/- 8% (range 0-20%). The only distinguishing morphologic finding associated with nephrotic range proteinuria was diffuse foot process effacement. No correlation between subepithelial deposits and proteinuria was observed. There were no other histologic differences between the nephrotic and non-nephrotic patients. Among these patients, the nephrotic syndrome appears best correlated with podocytopathy rather than subepithelial electron dense deposits, mesangial deposits, or mesangial hypercellularity.

Adult↗
PubMed2005

Pathology of lupus nephritis.

The glomerular pathology of lupus nephritis is the result of diverse immune insults which are probably of independent pathogenetic origins. Although lupus nephritis is looked upon as a classic example of immune complex-induced microvascular injury resulting from circulating DNA double stranded polynucleotide antigens/anti-DNA antibody complexes, other mechanisms, including in situ reactivity of free antibody with fixed antigens and the role of sensitized T-cells, are probably an important part of the picture. This complexity makes categorization of glomerular pathology into a clinically relevant classification an important goal so that our experiences can be reliably compared. This review describes the various glomerular lesions commonly encountered in lupus nephritis and, based upon data derived from experimental models, emphasizes the importance of understanding the clinical relevance of the reported morphology. We point out that the severity of glomerular damage is not merely the accrued result of immune complex induced injury to individual capillaries, but involves capillary necrosis and thrombosis, neither of which may have anything to do with immune complexes or immune aggregates. In fact, the segmental lesions of glomerular capillary necrosis and thrombosis may have a great deal to do with the response to therapy and the ultimate outcome of the patient. While discrete morphologic lesions such as mesangiopathy, acute inflammation, necrosis, thrombosis, epimembranous lesions and podocytopathy are readily described, it is important to note that any given case can represent any combination of these insults. In this context, the new proposed International Society of Nephrology Classification is presented and its strengths and weaknesses discussed.

Antibodies, Antinuclear↗
PubMed2001

Significance of histologic patterns of glomerular injury upon long-term prognosis in severe lupus glomerulonephritis.

BACKGROUND: Patients with systemic lupus erythematosus have a spectrum of glomerular disease, but the different patterns of glomerular injury identified within the general category of "severe" lupus glomerulonephritis are responsible for much of the morbidity and mortality in this disease. The glomerular injury patterns seen with severe lupus glomerulonephritis have been separated into distinct histopathologic groups to determine whether they can predict long-term patient outcome. METHODS: We analyzed the clinical follow-up of 85 patients participating in a controlled prospective therapeutic trial for the treatment of severe lupus glomerulonephritis conducted from April 1981 to December 1988, with an average follow-up of 10 years. Patients were classified according to the 1982 World Health Organization classification for lupus glomerulonephritis. RESULTS: During the course of follow-up [120 +/- 65 (SD) months], 60% of patients with category IV (diffuse proliferative glomerulonephritis) lesions entered a remission compared with only 38% of patients with category III (> or =50%, focal and segmental glomerulonephritis) lesions and 27% of patients with category Vc (> or =50%) and Vd (P < 0.05). Renal survival at 10 years was 75% for those with category IV lesions, 47% for patients with category Vc (> or =50%) and Vd, and 52% for patients with category III (> or =50%) lesions (P < 0.05). Based on multivariate analysis, patients with category III (> or =50%) or Vc (> or =50%) and Vd lesions had a relative risk of progression to end-stage renal disease 2.9 times that of category IV patients (P < 0.01), while the likelihood of entering a remission was 8.2 times greater for category IV patients (P = 0.0001). CONCLUSION: The histopathologic categorization among patients with severe lupus glomerulonephritis provides information relevant to their long-term outcome.

Adult↗
PubMed2000

Factors predictive of outcome in severe lupus nephritis. Lupus Nephritis Collaborative Study Group.

In 1992, we published the results of a prospective, controlled trial of aggressive therapy (high-dose prednisone plus oral cyclophosphamide alone or with plasmapheresis) in 86 patients with severe lupus nephritis. During this study, remission (serum creatinine < or =1.4 mg/dL [< or =123 micromol/L] and proteinuria < or =330 mg/d of protein) in renal disease occurred in 37 patients (43%). To assess the long-term effect of remission on patient and renal survival, we now report the results of our extended follow-up of these patients. After an average of 10 years of follow-up in the 86 patients, patient survival rates at both 5 and 10 years were 95% in the group that had a remission and 69% at 5 years and 60% at 10 years in the no-remission group (P < 0.001). Renal survival rates were 94% at both 5 and 10 years in the remission group compared with 46% at 5 years and 31% at 10 years in the no-remission group (P < 0. 0001). Features predictive of remission included stable renal function after 4 weeks on therapy, category IV lesion, lower chronicity index, white race, lower urine protein excretion level at baseline, and lower baseline serum creatinine level. The features predictive of end-stage renal disease were higher baseline serum creatinine level, presence of anti-Ro antibodies, and failure to attain a remission. Thus, in patients with the most severe forms of lupus nephritis, a remission of clinical renal abnormalities is associated with dramatic improvement in long-term patient and renal survival.

Adult↗
PubMed2000

The role of podocyte injury in the pathogenesis of focal segmental glomerulosclerosis.

The podocyte has diverse functions including glomerular filtration, biosynthesis and maintenance of the glomerular capillary architecture. It discharges these functions by virtue of a unique morphology, an intimate relationship with the capillary wall, and diverse synthetic and membrane specializations. Despite the complex role that it plays in glomerular function, the clinical manifestations of podocyte dysfunction are limited to proteinuria and renal insufficiency. Recurrent focal segmental glomerulosclerosis (FSGS) in renal transplants provides a unique opportunity to study the pathogenesis of FSGS in human beings, because the patients are monitored carefully to identify the onset of disease, the recurrence is presumed to have the same etiology as the primary disease, renal biopsy is a tool to study the pathogenesis of the lesion, and therapeutic intervention provides a mechanism to test pathogenesis. Pathologic studies have identified a proliferative lesion of the podocytes as the first sign of recurrent disease. The glomerular lesions evolve to form segmental glomerular scars with time. These findings and studies in experimental models of FSGS implicate podocyte injury in the pathogenesis of the recurrent disease. The cellular lesion (similar to the proliferative lesion of podocytes in recurrent FSGS), seen early in the course of primary FSGS suggests that the pathogenic sequence in recurrent FSGS also applies to primary FSGS. A soluble circulating factor that increases glomerular permeability and correlates with recurrence of FSGS has been identified in the pretransplant serum of patients with end-stage FSGS, but the mechanism of podocyte injury by this factor remains speculative. In any case, podocytes in the cellular lesion undergo morphologic changes and lose specialized functions seen in the normal mature cell, and these structural and functional abnormalities cause the permeability changes associated with proteinuria and destruction of glomerular filtration surface by scarring associated with loss of glomerular function.

Animals↗
PubMed1999

Focal segmental glomerulosclerosis: prognostic implications of the cellular lesion.

The cellular lesion (CELL), seen in some patients with primary focal segmental glomerulosclerosis (FSGS), comprises proliferation, hypertrophy, and pathologic changes in the cells overlying the glomerular scar. The prognosis of the cellular lesion was retrospectively studied in 100 patients with FSGS (43 had FSGS-CELL and 57 had FSGS without the cellular lesion (classic segmental scar [CS]). Patients with the FSGS-CELL lesion were more often black and severely proteinuric and developed more end-stage renal disease (ESRD). Nephrotic patients with FSGS-CELL (n = 39) were more proteinuric at presentation than patients with FSGS-CS (n = 36). ESRD developed more frequently in patients with the FSGS-CELL (17 of 39, 44% versus 5 of 36, 14%, P = 0.005), and patients with extensive FSGS-CELL (> or = 20% glomeruli) were mainly black (94%), severely nephrotic (67%, >10 g/d), and had a poor response to treatment (23% remission). In nephrotic patients, initial serum creatinine, interstitial expansion > or = 20%, and CELL independently predicted ESRD. However, the rates of remission in treated nephrotic patients with FSGS-CELL and FSGS-CS were the same (9 of 17, 53% versus 17 of 39, 52%), and patients in both groups who achieved a remission had a 5-yr survival of 100%. Steroid treatment was the only variable that predicted remission. Patients with the FSGS-CELL have an increased prevalence of ESRD, but the improved prognosis associated with remission is so significant that a therapeutic trial is warranted in all nephrotic FSGS patients, regardless of the presence of the cellular lesion.

Adult↗
PubMed1998

Renal pathology patterns in type II diabetes mellitus: relationship with retinopathy. The Collaborative Study Group.

BACKGROUND: The glomerular and retinal vessels are both affected in patients with type I and type II diabetes mellitus. However, the prevalence of the nodular form of diabetic glomerular sclerosis (Kimmelstiel Wilson lesion) and other forms of glomerular pathology including diffuse mesangial sclerosis and their clinical correlates in type II diabetes are less well known. In addition, although recent studies have suggested that non-diabetic glomerular disease was a common cause of proteinuria in type II diabetes, the prevalence of other diseases is unknown. The literature on this subject is clouded by clinical bias regarding patients with diabetes who undergo renal biopsy. METHODS: Glomerular and retinal pathology and clinical correlates were studied in 36 patients enrolled in a prospective clinical trial of patients with type II diabetes mellitus, proteinuria, renal insufficiency, and hypertension. RESULTS: Seventeen biopsies had diabetic glomerular sclerosis with Kimmelstiel Wilson nodules; 15 biopsies had glomerular changes characteristic of the diabetic state including enlarged glomeruli and an increase in mesangial matrix without Kimmelstiel Wilson nodules (mesangial sclerosis lesion); and two had other primary glomerular diseases (IgA and membranous nephropathy). Patients with Kimmelstiel-Wilson nodules had elevated serum creatinines compared to patients with mesangial sclerosis lesions, but there were no other significant differences. Patients with Kimmelstiel Wilson nodules had more severe overall retinopathy than those with mesangial sclerosis lesions (P = 0.0043): six of seven with proliferative retinopathy had Kimmelstiel Wilson nodules, and seven of the eight patients without retinopathy had mesangial sclerosis lesions. CONCLUSIONS: The two discrete patterns of glomerular pathology and the correlation between diabetic retinopathy and the Kimmelstiel-Wilson lesion but not the mesangial sclerosis lesion suggest that the Kimmelstiel Wilson and mesangial sclerosis lesions of diabetic glomerulosclerosis are caused by different pathogenetic mechanisms. In this study, diabetic glomerulosclerosis was responsible for the clinical renal abnormalities in 94%, of patients with type II diabetes mellitus.

Adult↗
PubMed1997

Juvenile rheumatoid arthritis in African Americans.

OBJECTIVE: To examine racial differences in disease expression in African American and Caucasian children with pauciarticular and polyarticular juvenile rheumatoid arthritis (JRA). METHODS: A retrospective chart review was conducted of 35 African American and 137 Caucasian children with pauciarticular and polyarticular JRA. RESULTS: African American children were significantly older than Caucasian children at the time of presentation. This was true both for the group as a whole and for each of the disease onset subtypes. African American children were less likely to have positive antinuclear antibody tests than Caucasian children. This finding paralleled a low incidence of uveitis in African American children. African American children were also more likely to have IgM rheumatoid factors (detected by latex agglutination) than Caucasian children. This was true even for African American children with pauciarticular JRA. CONCLUSION: There are significant phenotypic differences between African American and Caucasian children with JRA.

Adolescent↗
PubMed1996

The racial prevalence of glomerular lesions in nephrotic adults.

We retrospectively evaluated the prevalence of primary glomerular lesions in adults who had a renal biopsy for nephrotic proteinuria. From July 1975 to May 1994, 340 patients undergoing renal biopsies evaluated at Rush-Presbyterian-St Lukes Medical Center had the primary glomerular lesions of minimal-change disease, focal segmental glomerular sclerosis (FSGS), membranous glomerulonephritis (MGN), membranoproliferative glomerulonephropathy, immunoglobulin A nephropathy, and immunotactoid glomerulopathy. The patients had a mean age of 43 +/- 17 years, 57% were male, and 50% were white, 36% were black, 7% were of other race, and 7% were of unknown race. The distribution of lesions for black patients was minimal-change disease 14%, FSGS 57%, MGN 24%, membranoproliferative glomerulonephritis 2%, immunoglobulin A 2%, and immunotactoid glomerulopathy 1%; for white patients, the distribution of lesions was minimal-change disease 20%, FSGS 23%, MGN 36%, membranoproliferative glomerulonephropathy 6%, immunoglobulin A 8%, and immunotactoid glomerulopathy 6%. The prevalence of FSGS was significantly greater (P < 0.0001) and that for MGN, immunoglobulin A, and immunotactoid glomerulopathy was significantly less (P < 0.05) for black patients compared with white patients. In a logistic regression analysis, race remained the only significant predictor of FSGS (P = 0.0001), with black patients four times as likely to have FSGS as white patients. The distribution of lesions among white patients was similar based on gender, age, and biopsy period. For black patients the distribution was also similar based on gender and age, but over 20 years the incidence of FSGS increased from 39% (1975 to 1984) to 64% (1985 to 1994) (P < 0.01). Thus, significant racial differences in the distribution of primary glomerular lesions exists. This has important prognostic and therapeutic implications for nephrotic adults.

Adolescent↗
PubMed1996

Long-term outcome in systemic lupus erythematosus membranous glomerulonephritis. Lupus Nephritis Collaborative Study Group.

The pathology of membranous glomerulonephritis (MGN) in patients with systemic lupus erythematosus (SLE) may be complicated by superimposed glomerular inflammation and/or necrosis. This retrospective study examined whether various histologic patterns of glomerulonephritis (GN) seen on renal biopsy impact upon the prognosis of these patients. Clinical parameters at the time of biopsy were also studied, to determine which might serve as risk factors associated with renal and patient outcome. On the basis of renal biopsy findings, patients were stratified into three pathological study groups by using the World Health Organization (WHO) classification (11). Thirty-six patients had "pure' SLE MGN without (WHO Va) or with (WHO Vb) mesangial hypercellularity. Fifteen patients had SLE MGN with segmental endocapillary proliferation and/or necrosis in < 50% of glomeruli (WHO Vc < 50%). Twenty-eight patients had SLE MGN with endocapillary proliferation and/or necrosis in > or = 50% of glomeruli (MGN with segmental proliferation and/or necrosis in > 50%, WHO Vc > or = 50%, or MGN with superimposed diffuse endocapillary proliferation, WHO Vd). There were no significant differences in sex, age, or race among patients in the three study groups. There was a trend for increasing serum creatinine concentration, urine protein excretion, and diastolic blood pressure, and decreasing the third component of serum complement (C3) to be associated with increasing glomerular inflammation, and these differences were significant when Vc > or = 50% and Vd was compared with Va and Vb (P < 0.05). The 5- and 10-yr actuarial survival rates without reaching the study outcomes of death or renal replacement therapy for the three study groups were 86, 72, and 49% and 72, 48, and 20% respectively, and the differences between Va and Vb and Vc > 50% and Vd were significant (P < 0.05). SLE MGN has a heterogeneous course and outcome, and this variability is related to the extent and degree of glomerulonephritis seen on renal biopsy. The only clinical factor with an independent risk of reaching a study outcome was elevation of the initial serum creatinine concentration (Cox regression analysis). This predictive value appears to apply only to patients with the most severe forms of glomerulonephritis, suggesting that they may have a different natural history and/or a response to therapy than SLE MGN with less widespread glomerular inflammation and/or necrosis.

Biopsy↗
PubMed1995

Focal segmental glomerular sclerosis in adults: presentation, course, and response to treatment.

The authors performed a retrospective clinicopathologic study in 81 patients with primary focal segmental glomerular sclerosis (FSGS) to determine whether they could identify clinical or histologic features at presentation that could be predictive of outcome and response to therapy. Males constituted 58% of patients, and 53% were black. At biopsy the patients were 40 +/- 17 years old; 74% were nephrotic, and renal insufficiency was present in 62%. The average time from presentation to biopsy was 16 months, and the average total follow-up was 62 months. Nephrotic patients had a significantly poorer prognosis as compared with nonnephrotic patients (5- and 10-year survivals of 76% and 57% v 92% and 92%; P < 0.05). A multivariate analysis was done on histologic and clinical features at biopsy, assessing for risk factors leading to end-stage renal disease, showing only the serum creatinine and the degree of interstitial fibrosis to have a significant correlation. Thirty nephrotic patients received prednisone, with a treatment time of 5.5 +/- 4 months and a total dose of 5.9 +/- 2.9 g per course of treatment. Fifteen of these patients (50%) achieved a remission by 3.7 +/- 2 months (10 complete remission and 5 partial remissions), with all patients responding within 9 months. Only two patients had spontaneous remissions (both partial). The 5- and 10-year survival for patients in remission were both 100% as compared with 66% and 41% (P < 0.01), respectively, for nephrotic patients not in remission. No clinical feature at presentation of biopsy was predictive of response to therapy when a multivariate analysis was performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Renal vasculitis associated with ciprofloxacin.

We report two patients treated with ciprofloxacin who presented with acute renal failure. On renal biopsy, a necrotizing vasculitis was identified in addition to acute interstitial nephritis. Improvement in renal function resulted with the discontinuation of the antibiotic and the institution of immunosuppressive therapy.

Aged↗
PubMed1995

Primary focal segmental glomerular sclerosis in adults: prognostic value of histologic variants.

Primary focal segmental glomerular sclerosis (FSGS) is a clinicopathologic syndrome in which variable amounts of proteinuria are associated with the renal biopsy finding of segmental glomerular scarring in some, but not all, of the glomeruli. Additional histologic features have been described in FSGS, including the position of the scar relative to the vascular and tubular pole of the glomerulus, foam cells, hyalinosis, mesangial deposits of immunoglobulin M, diffuse mesangial hypercellularity, glomerular visceral epithelial cell hyperplasia and hypertrophy, and the extent of associated interstitial fibrosis and tubular atrophy. We performed a retrospective study on 81 patients with biopsy-proven, primary FSGS to determine whether any of the histologic features of FSGS correlated with renal function at the time of biopsy and the incidence of end-stage renal disease at follow-up. Sixty patients were nephrotic and 21 had nonnephrotic proteinuria. Only the degree of interstitial fibrosis correlated with the initial serum creatinine (r = 0.536) and none of the histologic features predicted the presence of nephrotic-range proteinuria at the time of biopsy. Segmental scars involved 21% +/- 14% of the glomeruli per biopsy specimen, but their position within the glomerulus was uniform in only 13% of the cases. Diffuse mesangial hypercellularity was present in 17% of the biopsy specimens, and glomerular epithelial cell lesions were present in 57% of the biopsy specimens. Multivariate analysis showed that only the degree of interstitial fibrosis predicted end-stage renal disease in all 81 patients and in the 60 patients with nephrotic-range proteinuria. The current data do not support different therapeutic approaches in primary FSGS based on histologic subtypes.

Adult↗
PubMed1995

Lupus nephritis.

Lupus nephritis is a major cause of morbidity and mortality arising from systemic lupus erythematosus. The pathology seen on renal biopsy and clinical features of renal involvement remain major prognostic factors and therapeutic guides. Serologic markers also correlate with disease activity, but more significantly, the identification of cationic and anti-endothelial cell antibodies in patients may have pathogenetic implications. Experimental studies demonstrating pathogenic roles for cationic nuclear antigens, cationic and anti-idiotypic antibodies, and genetic control of antibody production, are being transferred to the clinic. Duplication of these results in patients suggests that similar mechanisms are operative in humans. Insights gained from pathological studies will lead to new therapeutic strategies, but at present lupus nephritis therapy is based on nonspecific immunosuppression. Therapeutic trials testing several established and new modalities have been published in the past year, but they are anecdotal and lacking in controls.

Animals↗
PubMed1994

The fibrillary glomerulopathies.

Fibrillary glomerulopathy is a category of glomerular disease that is defined by the ultrastructural feature of organized deposits of extracellular, nonbranching, microfibrils. The best-known disease in this category is amyloidosis, but cryoglobulinemia, light chain deposition disease, systemic lupus erythematosus, immunotactoid glomerulopathy, and diabetic fibrillosis may have similar ultrastructural findings and comprise the differential diagnosis of the fibrillary glomerulopathies. Because they have disease-specific therapeutic and prognostic implications, differentiating among these entities is important for nephrologists and nephropathologists. To aid the physician, we will review the fibrillary glomerulopathies using an algorithm based on morphology, clinical features, and serologic assessment. We believe this approach will prove to be practical and useful to the practicing nephrologist.

Actin Cytoskeleton↗