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Biomedical subjects

M M Schwartz

Publications and source records attributed to M M Schwartz.

At least 37 records · Page 2Linked to original sources
PubMed1994

Primary focal segmental glomerulosclerosis: clinical course and response to therapy.

Primary focal segmental glomerulosclerosis (FSGS) is a lesion associated with a poor prognosis and results in end-stage renal disease after 5 to 10 years. Based on past experience, many nephrologists have considered primary FSGS a lesion that is steroid resistant and therefore are reluctant to offer steroids as treatment. Recent data, however, have demonstrated that patients with primary FSGS have a response to steroid therapy that is considerably better than had been described. Thus, it may be that nephrologists have been more "steroid reluctant" than the lesion is steroid resistant. To better understand this issue we review the clinical course and response to therapy in patients with primary FSGS.

Glomerulosclerosis, Focal Segmental↗
PubMed1994

Renal ablation acutely transforms 'benign' hypertension to 'malignant' nephrosclerosis in hypertensive rats.

The present studies examine the consequences of the hemodynamic changes associated with approximately 5/6 renal ablation in the spontaneously hypertensive rat (SHR), a strain that normally does not exhibit evidence of vascular and/or glomerular injury until late in life despite significant hypertension. Control SHR with intact renal mass demonstrated normal renal autoregulation and an absence of vascular or glomerular injury. Renal mass reduction resulted in an initial expected decrease in renal blood flow to the remnant kidney at 5 days (2.8 +/- 0.3 mL/min) compared with control SHR (8.1 +/- 0.7 mL/min) at a mean arterial pressure of approximately 160 mm Hg (P < .01). By 10 to 14 days after renal ablation, marked renal vasodilation was observed (renal blood flow 8.3 +/- 0.8 mL/min at mean arterial pressure of approximately 160 mm Hg) along with severe impairment of autoregulatory ability. Striking and florid vascular injury to interlobular arteries and afferent arterioles had also developed by 10 to 14 days after approximately 5/6 renal ablation in a pattern similar to that observed in "malignant" hypertension, despite systolic blood pressures that were not significantly different from those in control SHR (168.2 +/- 6.4 versus 165.6 +/- 4.7 mm Hg). An additional group of SHR that were made normotensive with a triple-therapy antihypertensive regimen before and after approximately 5/6 renal ablation also exhibited hemodynamic changes similar to those in the untreated rats at 10 to 14 days but did not develop significant vascular or glomerular injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The mesangium in the long-term remnant kidney model.

Hypertension, which develops during the course of the remnant kidney model (RK), plays a major role in the pathogenesis of glomerular injury. Morphologic studies have implicated mesangial injury and dysfunction in the pathogenesis of glomerular scarring in the hypertensive RK, but a separate role for mesangial injury has not been demonstrated in the absence of systemic hypertension. We studied glomerular injury and mesangial structure and function in a long-term (26 weeks) normotensive rat RK by using morphologic and morphometric studies and mesangial clearance of aggregated rate IgG (AggRaIgG). After right nephrectomy and infarction of two thirds of the left kidney (RK), the rats gained weight and developed mild but stable elevations of serum creatinine and urinary protein excretion as compared with the sham-operated controls (SHAM) over the course of the study. Systolic blood pressure was only mildly elevated (129 +/- 9 mm Hg versus 114 +/- 8 mm Hg, p < or = 0.05). Virtually all of the RK rats developed glomerular scarring, with segmental sclerosis in 8% +/- 8% and global sclerosis in 2% +/- 2% of the glomeruli, whereas the SHAM animals had no glomerular scarring, but we found limited morphologic evidence of mesangial cell injury in RK. The RK glomeruli were hypertrophied as compared with glomeruli in SHAM rats (glomerular diameter 199.3 +/- 15.2 microns versus 160.5 +/- 4.4 microns, p < or = 0.05), and the accompanying increase in capillary volume was caused by an increase in capillary length without a significant increase in diameter. Despite the glomerular hypertrophy and increased initial uptake in RK, the mesangial clearance of AggRaIgG was similar between RK and SHAM rats. We conclude that WKY rats with RK develop a progressive glomerulopathy characterized by segmental glomerulosclerosis, proteinuria, and mild hypertension. The normal mesangial clearance function and the absence of mesangial pathology in the hypertrophic remnant glomeruli mitigate against a role for mesangial injury in this form of experimental renal disease.

Animals↗
PubMed1993

Immunolocalization of tenascin and cellular fibronectins in diverse glomerulopathies.

Frozen samples of minimal change glomerulopathy (MCG), and of membranous, segmental and diffuse lupus glomerulonephritis (MGN, SGN, DLGN) were studied to assess the distribution of tenascin (Ten), and the extradomains A and B (EDA- and EDB-) and oncofetal (Onc-) isoforms of cellular fibronectin (cFn). Cryosections were immunostained by the ABC method with specific monoclonal antibodies. In MCG, mesangial Ten and EDA-cFn reactions were increased. In MGN, mesangial Ten and EDA-cFn staining was enhanced except in segmental scars; convincing reactions were seen in cases with membranous transformation; spikes stained strongly. In SGN, variably intense staining for Ten and all cFn isoforms was seen in glomerular necrosis, proliferation and crescents; parietal epithelium EDA-cFn staining was noted. In DLGN, strong and extensive mesangial Ten and EDA-cFn staining was seen as were focal EDB- and Onc-cFn reactions. Parietal cells with and without crescents stained variably with all Mabs. Obsolete glomeruli were unreactive save for rare periglomerular Ten rims. Interstitial inflammation and fibrosis in MGN, SGN and DLGN had moderate to strong Ten and EDA-cFn staining with rare traces of EDB- and Onc-cFn. We conclude that enhanced Ten and EDA-cFn is a potentially reversible response to glomerular injury whereas the expression of EDB- and Onc-cFn apparently result from necrosis and/or cellular proliferation which lead to scarring. And, while mesangial cells are the major source of these molecules, epithelial cells might also partake in their synthesis.

Antibodies, Monoclonal↗
PubMed1993

Membranous glomerulonephritis and malignancy.

The purpose of this review is to enhance the clinical awareness of the association between membranous glomerulonephritis and neoplasia. Controversy has persisted that has tended to minimize this association, therefore, we report our experience to shed some light on this controversy as well as to make diagnostic recommendations. One hundred seven adult patients with biopsy-proven membranous glomerulonephritis were selected for review. Twenty of these patients had a known secondary cause of membranous glomerulonephritis other than malignancy. Data were collected retrospectively on all these patients and nine were found who had or developed malignancy associated with membranous glomerulonephritis. Clinical data were analyzed to ascertain the onset of renal disease in relation to the malignancy as well as to determine the ultimate patient and renal outcome after treatment of the neoplasm. Of the 87 patients with presumed idiopathic membranous glomerulonephritis, nine (10.3%) had or developed a malignancy associated with their renal disease. The membranous glomerulonephritis was seen in patients with various solid tumors as well as hematologic malignancies. All patients presented with nephrotic-range proteinuria. Proteinuria manifested itself prior to or concomitantly with the diagnosis of the neoplasm in approximately 80% of cases. Follow-up data were available on seven patients: complete remission of proteinuria was seen in two patients associated with treatment of their tumors, one patient developed end-stage renal disease, and the remaining four patients had persistent proteinuria associated with tumor recurrence or metastasis. There appears to be a clear association between membranous glomerulonephritis and neoplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Irreproducibility of the activity and chronicity indices limits their utility in the management of lupus nephritis. Lupus Nephritis Collaborative Study Group.

Histological indices of renal pathology in lupus nephritis have been proposed as prognostic signs and as a method to quantitate therapeutic response. We tested the reproducibility of the activity (AI) and chronicity indices (CI) in the renal biopsies from 83 patients with lupus nephritis, enrolled in a controlled therapeutic trial. The AI/CI were calculated separately by four renal pathologists using published criteria. Pair-wise Spearman's rank correlation coefficient was used to examine the relationship among the scores of the four raters, and their degree of reproducibility was evaluated using the coefficient of reliability. The mean CI scores ranged from 2.84 to 4.61, and the mean AI ranged from 9.64 to 12.89. The correlation among the different pathologist's scores ranged from 0.44 to 0.63 for the AI and 0.60 to 0.76 for the CI. One pathologist (M.M.S.) rated the biopsies twice, and the correlation between the two ratings was 0.58 for the AI and 0.74 for the CI. Thus, the AI and CI calculated by different pathologists and the temporally separate observations of a single observer were only moderately correlated. The reproducibility of a single rating was low, showing a reliability coefficient of 0.48 for the AI and 0.57 for the CI. The low reliability coefficient suggests that the variability among pathologists was the result of interpretative differences. We conclude that the AI/CI are too subjective to be used as therapeutic guides or as prognosticators.

Atrophy↗
PubMed1993

The use of the automatic core biopsy system in percutaneous renal biopsies: a comparative study.

We describe our experience with the use of the automatic core biopsy system for percutaneous renal biopsy and compare this with our experience with a standard biopsy needle. Three hundred twenty-three biopsies were performed between June 1983 and January 1993. From June 1983 through October 1990, 232 biopsies were performed with the use of a standard biopsy needle (Tru-cut needle; Travenol Laboratories, Deerfield, IL) and from November 1990 through January 1993, 91 biopsies were conducted with the use of the automatic core biopsy system (Biopty gun and needle; C.R. Bard, Inc, Covington, GA). Biopsies performed prior to January 1990 were reviewed retrospectively, while those performed after January 1990 were reviewed in a prospective manner. The primary indications for renal biopsy were to evaluate proteinuria (48.9%) and renal manifestations of systemic lupus erythematosus (26.0%). The two groups of patients were similar with respect to sex, age, serum creatinine, and coagulation parameters. Material for light microscopy, immunofluorescence microscopy, and electron microscopy was obtained in 98.9%, 98.9%, and 97.8% of cases, respectively, with the use of the automatic core biopsy system, and these values did not differ significantly from those with the use of the standard needle (99.6%, 96.1%, and 97.8%). Significantly more glomeruli were obtained by light microscopy per biopsy specimen with the use of the automatic core biopsy system versus the standard needle (28 +/- 15 and 21 +/- 13, respectively; P < 0.0001). Complications were assessed and separated by severity. Total complications were observed in 13 patients (14.3%) with the automatic core device and in 31 patients (13.4%) with the standard needle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Reversible compensatory hypertrophy in rat kidneys: morphometric characterization.

Functional renal compensatory hypertrophy (RCH) in the uninephrectomized rat is completely reversible by transplantation in Brown Norway (BN) rats, while anatomic RCH is not. To determine the nephron element(s) responsible for persistent anatomic RCH, we performed morphometric analysis on perfusion fixed rat kidneys following renal function studies. In this model the function of renal transplants is not different from contralateral and unmanipulated control kidneys, and there is no histological evidence of rejection. Rats uninephrectomized for three or six weeks had larger glomeruli than controls, and after transplantation of a previously hypertrophied kidney into a rat with a normal or a solitary hypertrophied kidney, glomerular size returned to control levels. Increased glomerular capillary volume (CVCP) in kidneys with RCH was due to increased capillary length (LCP; 13.1 +/- 1.0 mm cf. 10.3 +/- 0.9, P < 0.01) without increase in capillary radius (RCP; 3.26 +/- 0.33 microM cf. 3.28 +/- 0.24). In contrast, return of CVCP to control levels in kidneys undergoing regression was associated with persistently elevated LCP (13.0 +2- 2.9 mm; native previously hypertrophied kidney; 12.2 +/- 0.9; transplanted previously hypertrophied kidney vs. 10.3 +/- 0.9, P < 0.01) and decreased RCP (2.79 +/- 0.10 microM and 2.73 +/- 0.09, cf 3.28 +/- 0.24, P < 0.01). RCH was associated with proportional increases in glomerular, tubular, and vascular-interstitial volumes while only elevated tubular volume persisted during regression. Altered glomerular capillary dimensions and increased tubular volumes acquired during renal RCH induced by unilateral nephrectomy persisted during complete functional regression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Renal amyloidosis and other fibrillar glomerular diseases.

Fibrillar glomerular diseases are defined by the ultrastructural accumulation of glomerular extracellular microfibrils or microtubules. The deposits have compositions particular to specific diseases, and it is important to distinguish among these clinical pathologic entities and their differing clinical implications. Amyloidosis and immunotactoid glomerulopathy are two examples of fibrillar glomerular diseases. Amyloidosis is a systemic disease in which the fibrils stain with Congo red and contain various biochemically distinct proteins that identify diseases with differing prognostic and therapeutic implications. Immunotactoid glomerulopathy is a primary glomerular disease, and the deposits contain immunoglobulins that do not stain with Congo red. In contrast to amyloidosis, division of immunotactoid glomerulopathy based on the immunoglobulin content or ultrastructural appearance of the deposits has no clinical relevance.

Amyloidosis↗
PubMed1993

Genetic predisposition to hypertension and microvascular injury in the remnant kidney model.

Genetic factors have been implicated in the development and progression of glomerulosclerosis and nephron loss in both experimental animals and in humans. The influence of a differing genetic predisposition to hypertension was examined in the remnant kidney (RK) model of progressive glomerulosclerosis. Dahl salt-sensitive (S) and salt-resistant (R) rats fed a normal salt diet underwent either sham surgery or approximately 5/6 renal ablation and were studied 2 to 3 weeks later. Renal ablation resulted in significantly more severe hypertension in RK-S rats (205 +/- 6.3 mm Hg, mean +/- SEM) compared with RK-R rats (153 +/- 3.5 mm Hg; p < 0.01). Renal autoregulatory ability, a protective mechanism against renal transmission of systemic hypertension, was normal in both S and R rats with intact renal mass. Renal ablation resulted in similar impairments of renal autoregulatory ability in both strains. However, striking differences in the severity of renal microvascular and glomerular injury were observed between the remnant kidneys of S and R rats, paralleling the differences in the severity of hypertension. The RK-S rats exhibited acute fibrinoid necrosis and thrombosis of glomerular capillaries, arterioles, and small arteries, whereas only mild segmental glomerulosclerosis lesions were observed in a small percentage of glomeruli in the RK-R rats. The intact kidneys of both strains were essentially free of glomerular or vascular lesions. These data suggest that a genetic predisposition to hypertension is a major determinant of the severity of hypertension that follows severe reduction of renal mass and the severity of the resulting hypertension, in turn, critically influences the severity of glomerular injury in the RK model.

Animals↗
PubMed1993

Role of glomerular epithelial cell injury in the pathogenesis of glomerular scarring in the rat remnant kidney model.

We investigated the roles of glomerular epithelial cell (GEC) pathology and dysfunction in the pathogenesis of glomerular scarring and attempted to separate them from direct hypertensive injury in the 5/6 nephrectomy (RK) model of glomerular injury. Male WKY rats weighing 200 g were studied 6 weeks after RK, when approximately one-half had developed systemic hypertension (systolic blood pressure > or = 150 mm Hg) (HT), and one-half were normotensive (NT). The incidence of glomerular necrosis and scarring was greatest in the HT rats (P = 0.0259), and vascular necrosis was only seen in 4 of 11 HT rats. The RK group had increased glomerular diameters (HT, 174 mu mean; NT, 171 mu; sham, 142 mu; P = 0.0014 by analysis of variance). There was foot process effacement in the HT and NT groups (HT, 104 filtration slits/100 mu glomerular basement membrane; NT, 112 mu; sham, 143 mu; P < 0.005 by analysis of variance), but GEC separation from the glomerular basement membrane was not significant in either HT or NT rats. GEC function was determined from protamine-heparin aggregate disappearance curves, and the curves, representing GEC endocytosis, were not different in either HT or NT groups compared with the sham-operated groups. These findings suggest that GEC function is preserved in RK, and the changes in glomerular size and GEC morphology are nonlethal and adaptive. The morphological appearance of the acute glomerular and vascular lesions and their presence only in HT animals is consistent with a hypertensive pathogenesis. The glomerular sclerosis seen in both HT and NT may result from either resolution of acute lesions with scarring and/or adaptive changes in glomerular structure and cellular functions other than the GEC clearance function we studied.

Animals↗
PubMed1993

Comparison of glomerular injury in juvenile versus mature rats in a remnant kidney model.

Glomerular compensatory hypertrophy and hypertension (HT) are two factors that have been implicated in the progression of renal disease after nephron loss. Because glomerular compensatory hypertrophy is different in young and mature animals, we studied the effects of 5/6 nephrectomy (RK) in juvenile (5 to 7 weeks of age) and mature (15 to 16 weeks) male Wistar-Kyoto rats to separate the effects of HT from normal growth and glomerular compensatory hypertrophy. The kidneys were perfusion fixed, glomerular pathology was documented, and glomerular diameter and capillary dimensions were determined by standard morphometry. Both groups developed comparable degrees of proteinuria and elevated serum creatinine level when compared with the sham operated controls (SHAM). Although the Wistar-Kyoto rat is "resistant" to the development of HT, 18 of 30 juvenile RK and 3 of 12 mature RK rats developed systolic HT (> or = 150 mm Hg). Acute glomerular necrosis was seen only in the HT rats (9 of 18 juvenile and 2 of 3 mature), whereas glomerular sclerosis was seen in both HT (18 of 18 juvenile and 3 of 3 mature) and normotensive rats (4 of 9 juvenile and 3 of 9 mature). Glomerular diameter was greater in the SHAM mature than SHAM juvenile rats (165 +/- 7 microns vs 142 +/- 12 microns, p < 0.05), but the proportional increase in glomerular diameter after RK was comparable in the juvenile (20%) and mature (19%) RK rats. Increased capillary volume resulting from normal glomerular growth (compare SHAM juvenile with SHAM mature) was due to increased glomerular capillary length (LCP).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗