Biomedical subjects
Publications and source records attributed to G Eknoyan.
We have described a case, with renal biopsy findings and serologic studies, of a patient who had the nephrotic syndrome after sustaining multiple bee stings and who demonstrated a favorable response to steroid therapy. Bee stings have previously been implicated in the development of this syndrome, though the reported cases in the literature are poorly documented.
The platelet content of adenosine triphosphate (ATP), adenosine diphosphate (ADP), serotonin and ouabain-insensitive, magnesium-dependent adenosine triphosphatase (ATPase) was determined in patients with chronic renal failure, patients on chronic hemodialysis, and kidney transplant recipients. Platelet ATP content was normal in all. By contrast, ADP content, expressed in mumol/10(11) platelets, was significantly lower in renal failure: 1.82 +/- 0.96 compared to 2.51 +/- 0.97 in normals (p less than 0.05), but not in dialyzed or transplanted patients; 2.27 +/- 0.96 and 1.87 +/- 0.87, respectively. The mean content of serotonin was also significantly lower in renal failure patients: 0.52 microgram/10(9) platelets as compared to 0.90 microgram/10(9) platelets in normals (p less than 0.05) but was not significantly different in dialyzed and transplanted patients. ATPase was significantly lower in renal failure: 3.13 +/- 1.2 mumol Pi/10(9) platelets in whole suspension and 0.71 +/- 0.22 Pi/mg protein/h in membrane preparation compared to 4.74 +/- 1.1 and 1.18 +/- 0.19, respectively, in normals, and was significantly lower in dialyzed and transplanted patients. Experimental azotemia (BUN 65-86 mg/100 ml), induced by the oral ingestion of urea 2-3 g/kg body weight over 24 h, failed to induce any of these abnormalities. The abnormality in platelet ADP and serotonin content in renal failure paralleled the functional platelet defects which characterize these patients and were reversible following dialysis and transplantation.
The effect of secondary HPT on PMN function, as assessed by CL, was studied in two groups of patients. Group 1 comprised seven patients with no clinical evidence of secondary HPT and mildly elevated levels of serum iPTH (mean 2.7 +/-0.9 microleq/ml), and group 2 had six patients with clinical and radiological evidence of secondary HPT and higher ( p < 0.001) levels of iPTH (mean 26 +/- 7 microleq/ml). PMNs from group 2 patients demonstrated 68% +/- 9 augmented CL in the presence of autologous serum. Cross-incubation studies showed that sera from group 2 patients induced augmented CL in normal PMNs. In contrast, PMNs from group 2 patients showed reduced CL in the presence of normal serum. The augmenting effect of group 2 sera did not correlate with the level of calcium, phosphorus, creatinine, or BUN in serum. After successful subtotal parathyroidectomy, evident by the decrease of serum iPTH levels, both the CL of group 2 PMNs and the ability of group 2 sera to induce augmented CL in normal PMNs decreased (p < 0.025). These results suggest that secondary HPT is directly or indirectly responsible for the altered leukocyte function in some patients with uremia, particularly those with marked elevation of iPTH.
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Two patients had transient deterioration of renal function during acute infectious states while receiving indomethacin. Neither patient was in septic shock; renal function deteriorated at a time when clinically the infection was improving and both patients improved when indomethacin was discontinued, with return of renal function to baseline. Indomethacin inhibits prostaglandin synthesis and has been shown to reduce glomerular filtration and alter renal hemodynamic autoregulation. In susceptible patients these effects may be clinically significant. Careful monitoring of renal function in such patients requiring indomethacin therapy is warranted.
A relatively mild nonoliguric acute renal failure developed early in the course of daily rifampin treatment in a 54-year-old man who was receiving concomitant steroid therapy. The renal lesion was an acute interstitial nephritis characterized by tubular dysfunction:inability to concentrate urine, increase in fractional excretion of sodium and uric acid, and glycosuria with normal blood glucose values. All abnormalities resolved promptly upon withdrawal of rifampin while steroid therapy was gradually reduced. The documents the fact that rifampin-induced nephropathy can occur in the course of a continuous daily regimen and may be favorably influenced by steroid administration.
The impact of aging on the severity of chronic immune-complex glomerulonephritis was studied in 144 patients from whom diagnostic renal biopsies were obtained over a 3-year period. Glomerulonephritis was related to an antecedent streptococcal infection in nine of these patients. In 58, glomerulonephritis occurred in association with a systemic disease; 27 of these had lupus erythematosus. At the time of the renal biopsy, serum creatinines were more frequently abnormal in men over 40 years of age. Similarly, histological evidence of irreversible glomerular injury was more evident in men over 40. Histological indices of renal glomerular injury correlated with the presence of intense fluorescent antibody reactions specific for C3 and C4 and IgG in the glomeruli. High serum Clq binding activities (Clq BA), an indication of the presence of circulating immune complexes, also were found significantly more often in males over 40. High serum Clq BA correlated with renal functional and biopsy evidence of severe glomerulonephritis. The renal biopsies in 89 cases were tested with fluorescein-conjugated heat-aggregated IgG (FAIgG) to determine how many contained focal immunoglobulin deposits with antiglobulin activity. Antiglobulins were detected in glomeruli of 24 patients and were found significantly more often in biopsies which revealed histological evidence of severe and irreversible histological injury. Binding of FAIgG was not selectively associated with any sex or age groups. Thus, detection of circulating immune complex-like materials in sera and the presence of glomerular deposits with antiglobulin activity were both features associated with severe glomerular injury. Both correlated with the quantity of complement deposited in the glomeruli. But only serum Clq binding activity was age and sex related. Similarly, in cancer patients, abnormal Clq BA were found more frequently in sera of older men with cancer but not in age- and sex-matched controls. Examination of selected sera by sucrose density gradient ultracentrifugation revealed that the complexes from cancer patients were relatively small (less than 19S greater than 7S) whereas those in most nephritis patients were heterogeneous in size. Sera with relatively high Clq binding activity from patients with chronic glomerulonephritis tended to contain relatively greater quantities of Clq binding materials sedimenting more rapidly than 19S.
Effects of renal failure and experimental azotemia on in vitro leukocyte migraton were studied. Migration of normal leukocytes in sera from patients with untreated renal failure was regularly decreased, while sera from patients on chronic dialysis exerted no inhibitory effect. Serial sera obtained from two patients starting chronic dialysis exhibited a gradual decrease and ultimate disappearance of the serum inhibitory effect. Experimental azotemia serum supported increased migration of normal leukocytes. Leukocytes from renal failure patients migrated normally when incubated in autologous uremic serum or in normal homologous serum. These results provide evidence that serum from untreated renal failure patients inhibits the in vitro migration of normal leukocytes. This inhibitory capacity is apparently correctable by hemodialysis.
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Localization of fluorescein-conjugated heat-aggregated IgG (FA IgG) was demonstrated by immunofluorescence in renal glomeruli of 16 of 69 patients with glomerulonephritis. FA IgG bound more frequently in kidney biopsies from patients with diffuse glomerulonephritis and depressed renal function, and localized selectively in glomeruli that contained heavy deposits of IgM, C3, and C4. The factors that caused FA IgG to bind were specifically reactive with the Fc piece of the IgG molecule and were resistant to 56 degrees C heat for 30 minutes. Localization of FA IgG in the kidney did not correlate with the presence of soluble immune complexes or detectable antiglobulin antibodies in the sera. Binding of FA IgG was also seen in glomeruli and arteries of 18 of 21 kidney allografts studied at the time of impending rejection. But the factors responsible for binding FA IgG in the allografts were heat labile and thus could have been C1q. Although the role of these "antiglobulins" in the immunobiology of glomerulonephritis remains unknown, the fact that they occurred mainly in patients with relatively severe glomerular injury suggests that they could play some part in promoting renal glomerular injury.
A patient with systemic lupus erythematosus (SLE) and a patient with an immune complex disease resembling Goodpasture's syndrome were treated with cyclophosphamide, prednisone and repeated plasma exchanges. Circulating immune complexes decreased, and symptoms of central nervous system disease remitted for up to 15 to 20 days after plasma exchange in the patient with SLE. In vitro lymphocyte blastogenic responses to antigens were also transiently increased on two occasions following treatment. In the second patient, decreases in circulating immune complexes and clinical improvement were ascribed chiefly to immunosuppressive drug treatment. Serum antibody to keyhole limpet hemocyanin was relatively unaffected by plasma exchange in both patients. These results suggest that plasma exchange may help to deplete circulating immune complexes or alter the equilibrium between soluble antigen and antibody which causes complexes to form and circulate. It may be less effective in reducing circulating antibody levels in patients who continue to produce new antibody.
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