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Biomedical subjects

D Glicklich

Publications and source records attributed to D Glicklich.

At least 37 records · Page 2Linked to original sources

Effect of long-term normalization of serum complement levels on the course of lupus nephritis.

PURPOSE: We compared the long-term outcome of patients with lupus nephritis in whom normalization of complement levels (CH50) was sustained by adjustment of immunosuppressive therapy to those patients with persistently low complement levels despite similar immunosuppression in whom therapy was adjusted solely on the basis of clinical disease activity. PATIENTS AND METHODS: Thirty-nine female patients with lupus nephritis recruited from 1972 to 1979 were prospectively studied (mean follow-up, 116.7 +/- 11 months). Entry criteria included initial renal biopsy, low CH50, and elevated anti-DNA antibody levels. A second biopsy was performed in 24 patients after an interval of 40.6 +/- 5 months. Treatment was started with prednisone (1 mg/kg/day). Azathioprine at a dose of 1.5 to 2.0 mg/kg/day was added if complement was not normalized by prednisone alone. Twenty-five of 39 patients had normal complement levels within six months (Group 1), and immunosuppressive therapy was tapered but continuously readjusted to the lowest dosage that preserved normal CH50 and maintained clinical remission. Eight of these 25 patients subsequently became persistently hypocomplementemic due to inadequate drug intake (Group 1B), whereas the complement levels continued to be controlled in the other 17 patients (Group 1A). Despite similar therapy, the remaining 14 patients did not achieve normalization of complement within the initial six months of therapy, and therefore future treatment decisions were based solely on clinical symptoms (Group 2). Renal pathologic lesions were classified according to World Health Organization criteria and a semi-quantitative chronicity index. RESULTS: During the first six months, there were no significant differences in clinical or histologic features between patients in whom complement levels were controlled and patients in whom complement levels were not controlled. After a mean observation period of 10 years, however, patients with consistent normalization of complement (Group 1A) did much better than patients with only short-term complement control (Group 1B) or persistent hypocomplementemia (Group 2). Both groups with low complement levels had a similar outcome with significantly worse kidney and patient survival. Life-table analysis demonstrated that the differences in outcome between complement-controlled and complement-uncontrolled groups became apparent only after five or more years of follow-up. Patients with a low chronicity score on initial biopsy whose complement level was controlled did uniformly well with no renal failure or death. (ABSTRACT TRUNCATED AT 400 WORDS)

Azathioprine↗

Successful transplantation after conversion of a positive crossmatch to negative by dissociation of IgM antibody.

Preliminary crossmatching usually eliminates highly sensitized patients from consideration for renal transplantation. However, if the crossmatch is positive because of the presence of IgM antibody, this activity can be eliminated by treatment with the reducing agent Dithiothreitol (DTT). Successful transplantation may then be possible in patients whose crossmatch is positive due to the presence of IgM antibody. After treatment with DTT, the sera of 25 highly sensitized patients were measured for cytotoxicity against a selected panel of 40 cells. Those whose high %PRA could be attributed to blood transfusions or previous transplants did not change with DTT. Only two patients who had developed high panel reactivity, without a clear cause, had little reactivity remaining after DTT treatment of their sera. To select patients whose crossmatch might be rendered negative by DTT treatment, we developed a "minipanel" screening protocol. Patients whose monthly PRA cells increased greater than 30% from baseline had their serum samples treated with DTT to reduce IgM. The treated sera were tested against a panel of six cells. If there was little or no cytotoxicity, it was assumed that IgM antibody was responsible for the positive crossmatches. All subsequent cadaver donor crossmatches were done with and without DTT treated sera. Five patients (2 living-related; 3 cadaver) with current crossmatches positive before, but negative after, DTT treatment continue to have functioning kidneys 3-15 months after renal transplantation. There were no hyperacute rejections. We conclude that patients with IgM antibody can be successfully transplanted if they have a negative cross-match after reduction of IgM antibody in their serum samples. A "minipanel" helps to identify patients who will benefit from DTT treatment.

Adult↗

Possible genetic predisposition to idiopathic focal segmental glomerulosclerosis.

HLA-A, B, and DR antigen frequencies were studied in a group of 57 patients to determine possible inborn susceptibility to idiopathic focal segmental glomerulosclerosis (FSGS). There were 34 white patients and 23 black patients, most of whom had nephrotic syndrome and later developed renal failure. HLA-DR4 was significantly increased in both patient groups when compared with their respective control groups. This association has not been previously reported. Of note, the association with DR4 was most striking in patients with adult onset disease (in blacks, relative risk equals 5.2; in whites, relative risk equals 5.8). No other antigen was increased in both patient groups but HLA-A28 was increased in blacks. These data support the notion of genetic predisposition to focal segmental glomerulosclerosis in two different ethnic groups.

Adolescent↗

HLA associations in heroin-associated nephropathy.

Heroin-associated nephropathy (HAN) occurs almost exclusively in black heroin abusers, suggesting a genetic link to the disease. To further study this possibility, the frequencies of HLA-A, B, C, and DR antigens were determined in a group of 47 black patients with HAN. Included in the analyses is a subgroup of 16 patients with biopsy-proven focal glomerulosclerosis. Patient frequencies were compared with three separate control populations, the first a normal black population from New York City, the second from a national registry, and the third a group of blacks with idiopathic focal glomerulosclerosis. Only the frequency of HLA-BW53 was consistently increased significantly in the patients as compared with the control groups. This finding supports the notion that a genetic predisposition may exist in the addicted population for the development of renal disease.

Adult↗

The effect of the referring dialysis center on renal transplant results.

Between 1/1/76 and 12/31/86, 448 patients underwent transplantation (360 first transplants). Of these, 286 (230 first) were referred by 5 dialysis centers, each referring more than 40 recipients. The remainder were referred by a large number of centers. Using our 5 largest referral centers, we studied the effect of dialysis center on graft and patient survival. There was no difference between dialysis centers in patient survival. Actuarial graft survival differed significantly for all cadaver transplants and for first cadaver transplants (P less than 105). Significant differences persisted when groups were subdivided by type of immunosuppression (azathioprine vs cyclosporine). Demographic (age, race, cause of renal disease) and immunologic (transfusions, PRA, matching) differences between groups did not explain the difference in graft survival. We conclude that referring dialysis center is a previously unrecognized factor affecting transplant outcome. Further studies with larger numbers will be required to determine the underlying reasons for ths phenomenon.

Adult↗

2,8-dihydroxyadenine urolithiasis: report of a case first diagnosed after renal transplant.

We report a case of homozygous adenine phosphoribosyl transferase (APRT) deficiency associated with 2,8-dihydroxyadenine stones recurrent in a patient with a renal transplant. The disease was diagnosed 23 years after the initial episode of renal colic. At that time the disease was unknown. Our patient is only the second case of this disorder reported from the United States. Correct diagnosis is important because long-term maintenance with allopurinol and a low purine diet can effectively prevent stone formation and renal failure.

Adenine↗

Individualization of immediate posttransplant immunosuppression. The value of antilymphocyte globulin in patients with delayed graft function.

In patients with delayed graft function (DGF), the use of cyclosporine (CsA) has been reported to prolong DGF, increase the number of required dialyses, increase the duration of hospitalization, and be associated with decreased graft survival. Routine postoperative antilymphocyte globulin (ALG) use has been advocated, but ALG is associated with increased viral infection. We studied outcome of individualization of immunosuppression. Between 11/84 and 8/86, first-cadaver transplant recipients whose serum creatinine (Cr) fell greater than or equal to 30% in the first 24 hr (immediate function) were started on CsA and prednisone (P) (group 1, n = 26). The remainder were randomized to P and azathioprine (group 2, n = 32) or P and ALG (group 3, n = 26), and switched to CsA when serum Cr fell greater than 30% (minimum 5 days ALG for the ALG group). P taper was the same in all groups. Patients with DGF (groups 2 and 3) had longer preservation time and higher peak PRA (P less than .05) than group 1. Groups were otherwise equivalent. One and 2-year patient survival was 96% (3 cardiovascular deaths; all with functioning grafts). One-year graft survival was 87% for group 1, 87% for group 2, and 82% for group 3(NS). In patients requiring dialysis, mean day off dialysis was 12 +/- 3 in both groups 2 and 3. Mean hospital stay was 12.5 +/- 1.3 days for group 1, 21.6 +/- 2.1 days for group 2 (P less than .05 vs. 1 & 3), and 14.5 +/- 1.2 days for group 3 (NS vs. 1). The increased hospital stay for group 2 patients was mainly due to increased in-hospital rejections: 75% for group 2, (P less than .05 vs. group 1 [35%], and group 3 [11.5%]). In addition, more group 2 in-hospital 1st rejections were steroid resistant as compared to group 1; 46% group 1 patients have remained rejection free as compared to 0% group 2 (P less than .05 vs. 1 and 3) and 35% of group 3 (P less than .05 vs. 1 and 2). Mean serum creatinine at 6-12 months remained higher in patients with DGF (group 1 P less than .05 vs. 2 and 3). Rejection was the major cause of graft loss in all groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗

Timing of cyclosporine administration in patients with delayed graft function.

Cyclosporine in renal transplant recipients with delayed graft function (DGF) has been reported to decrease graft survival and prolong both DGF and hospitalization. In some centers, antilymphocyte globulin (ALG) has been used perioperatively to obviate these problems, but ALG is associated with increased viral infections. In this study, first cadaver transplant recipients with a fall in serum creatinine level of greater than or equal to 30% in the first 24 hr were started on prednisone (P) and cyclosporine (Group 1, n = 18). Those whose creatinine level did not fall were started on P and azathioprine (Group 2, n = 23) and switched to P and cyclosporine when serum creatinine fell 30%. One-year patient survival was 98%. One-year graft survival was 83% for both Groups 1 and 2 (NS). Results were compared to historical controls with DGF who received P and cyclosporine (Group 3, n = 19). Patients with DGF and requiring dialysis had fewer dialyses (P less than 0.05) and a shorter hospital stay (P less than 0.05) if started on azathioprine, as compared to those started on cyclosporine. Patients with DGF had a higher serum creatinine at 12 months than those with immediate function (P less than 0.05). We conclude that withholding cyclosporine until DGF is resolving decreases the duration of dialysis, decreases hospital stay, and without the use of prophylactic ALG, is associated with graft survival equivalent to that in patients with immediate function.

Adult↗

Recurrent membranoproliferative glomerulonephritis type 1 in successive renal transplants.

We report a man who developed renal failure due to membranoproliferative glomerulonephritis (MPGN) type 1 which recurred in two cadaveric kidney transplants. This is the third such case in the literature. Nephrotic syndrome developed within 1 month following transplantation and histologic evidence of disease recurrence was documented in both kidneys 2 months after transplantation. Both grafts failed within 18 months. Factors which determine disease recurrence remain obscure.

Adult↗

Renal failure due to lymphomatous infiltration of the kidneys. Report of three new cases and review of the literature.

Three new cases of renal failure due to lymphomatous infiltration of the kidneys are described and the clinical features of 14 similar patients in the literature are reviewed. The diagnosis of renal failure secondary to lymphomatous infiltration was made by ruling out other causes of renal failure and demonstrating prompt improvement in renal function after systemic chemotherapy or local irradiation of one or both kidneys. Histiocytic lymphoma was the most common underlying disease. In the setting of diffuse lymphoma with other causes of renal failure reasonably excluded, radiographic demonstration of enlarged kidneys without obstruction suggests the need for intensive combination chemotherapy in most cases.

Aged↗