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S Hariharan

Publications and source records attributed to S Hariharan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Polyoma virus infection after renal transplantation. Use of immunostaining as a guide to diagnosis.

BACKGROUND: Polyoma virus infection is characterized by lymphocytic interstitial infiltrate in the kidney, and it mimics acute rejection. The purpose of this study is to estimate renal allograft outcome with this infection and characterize the lymphocytic infiltrates in polyoma virus-infected renal allografts. METHODS: Patients who had polyoma virus inclusions in renal allograft biopsies were identified. Other viral inclusions were excluded by immunohistochemistry. The lymphocytic infiltrates of six cases of polyoma virus infection were compared with six cases of definite acute rejection by immunostaining for T and B cells. RESULTS: There were 10 cases of polyoma virus infections in renal transplant recipients. Immunosuppressants consisted of mycophenolate mofetil with tacrolimus in eight cases and mycophenolate mofetil with cyclosporine in two. The median time of diagnosis of polyoma virus infection after transplantation was 9.5 months, and the time to graft failure after the diagnosis was 4 months. Reduced allograft survival was seen in patients who had polyoma virus infection. Immunostaining for T and B cells revealed marked increase in the B cells (CD20) in renal allografts with polyoma virus infection of 21% (range, 5-40%) compared with 6% (range, 0-10%) in those with acute rejection (P=0.039). Reduced cytotoxic T cells (TIA-1: median, 7%; range, 2-15%) were seen in polyoma virus-infected allografts compared with 24% (range, 15-30%) in those patients who had acute rejection (P=0.0159). CONCLUSION: Irreversible graft failure is more prevalent with polyoma virus infection. Enhanced immunosuppressants with mycophenolate mofetil with tacrolimus may play a role in the development of this infection. An increase in CD20 and a decrease in cytotoxic T cells in allografts is characteristic of polyoma virus infection.

Acute Disease↗
PubMed2001

Evolution of immunosuppression and continued importance of acute rejection in renal transplantation.

As steady improvement in short-term kidney graft survival and long-term outcomes prolongs the lives of transplant patients, responsibility for their care is shifting away from transplant specialists and into the hands of community nephrologists. Therefore, community nephrologists need to have a deeper understanding of immunosuppressive therapies than ever before. Pharmacologic immunosuppression has been continuously evolving over the past two decades. Azathioprine was introduced in the early 1960s. Introduction of cyclosporine (CsA) in 1983 revolutionized short-term outcomes after renal transplantation. The first monoclonal antibody immunosuppressant, OKT3, was introduced in 1986. The 1990s saw the introduction of a number of important new agents, including mycophenolate mofetil (MMF), tacrolimus, and a microemulsion CsA, as well as two new monoclonal antibodies. Combinations of these new agents, along with improving clinical care, have produced 1-year patient survival approaching 100% and graft survival exceeding 90%. The newest class of agents, the first of which is sirolimus, is called target of rapamycin (TOR) inhibitors and is used with CsA for maintenance therapy. Immunosuppressive drug therapy after kidney transplantation continues to evolve. There is a variety of pharmacologic combinations from which to choose, based on immunologic risk and side effect profiles. As new regimens are developed, ongoing communications between the transplant center and community nephrologists will be required to implement therapeutic changes and optimize patient care successfully.

Graft Rejection↗
PubMed2001

Long-term kidney transplant survival.

With improvements in short-term kidney graft survival, focus has shifted towards long-term survival. There has also been a substantial improvement in long-term survival as measured by kidney half-life. Long-term graft failure is secondary to chronic allograft nephropathy (CAN), recurrent disease, and death with a functioning graft. CAN is secondary to a combination of chronic rejection, chronic cyclosporine toxicity, and/or donor kidney disease. Risk factors for chronic rejection have been attributed to both immunological and nonimmunological causes. With a marked reduction in acute rejection rates-an important risk factor for CAN-there is a substantial improvement in kidney half-life. There are still nonimmunological factors, such as donor age, that adversely affect long-term graft survival. In addition, African-American recipients continue to have a shorter graft half-life. Recurrent disease is becoming an important cause of late graft failure. Despite the introduction of various potent immunosuppressive agents, there has been little or no impact on the prevalence as well as progression of recurrent diasease. With the reduction of acute rejection rates and improved short- and long-term graft survival, further improvements of long-term graft survival will be an important focus in the 21st century.

Diabetic Nephropathies↗
PubMed2000

Human parvovirus B19 infection presenting as persistent anemia in renal transplant recipients.

BACKGROUND: Immunosuppression cannot be achieved without immunosuppressive effects. Human Parvovirus infection is known to occur after organ transplantation. We present our experience with Parvovirus infection in two cases. METHODS AND RESULTS: Two kidney transplant recipients developed symptomatic anemia requiring blood transfusions. Common causes of anemia, such as gastrointestinal bleeding, iron/vitamin deficiencies, hemolysis, and drug toxicities, were ruled out. A peripheral smear revealed low reticulocyte count. Bone marrow examination showed hypoplastic bone marrow with intranuclear inclusions suggestive of human Parvovirus. This was confirmed by immunohistochemical analysis. Treatment with i.v. immunoglobulin G resulted in a dramatic sustained response. Transplant kidney function remained stable. CONCLUSION: Human Parvovirus infections should be considered in immunosuppressed individuals with anemia with poor bone marrow response. Bone marrow examination can reveal viral inclusions and can be confirmed by immunohistochemical analysis. Intravenous immunoglobulin G results in resolution of anemia.

Adult↗
PubMed2000

Improved graft survival after renal transplantation in the United States, 1988 to 1996.

BACKGROUND: The introduction of cyclosporine has resulted in improvement in the short-term outcome of renal transplantation, but its effect on the long-term survival of kidney transplants is not known. METHODS: We analyzed the influence of demographic characteristics (age, sex, and race), transplant-related variables (living or cadaveric donor, panel-reactive antibody titer, extent of HLA matching, and cold-ischemia time), and post-transplantation variables (presence or absence of acute rejection, delayed graft function, and therapy with mycophenolate mofetil and tacrolimus) on graft survival for all 93,934 renal transplantations performed in the United States between 1988 and 1996. A regression analysis adjusted for these variables was used to estimate the risk of graft failure within the first year and more than one year after transplantation. RESULTS: From 1988 to 1996, the one-year survival rate for grafts from living donors increased from 88.8 to 93.9 percent, and the rate for cadaveric grafts increased from 75.7 to 87.7 percent. The half-life for grafts from living donors increased steadily from 12.7 to 21.6 years, and that for cadaveric grafts increased from 7.9 to 13.8 years. After censoring of data for patients who died with functioning grafts, the half-life for grafts from living donors increased from 16.9 years to 35.9 years, and that for cadaveric grafts increased from 11.0 years to 19.5 years. The average yearly reduction in the relative hazard of graft failure after one year was 4.2 percent for all recipients (P<0.001), 0.4 percent for those who had acute rejection (P=0.57), and 6.3 percent for those who did not have acute rejection (P<0.001). CONCLUSIONS: Since 1988, there has been a substantial increase in short-term and long-term survival of kidney grafts from both living and cadaveric donors.

Adult↗
PubMed2000

Phenyltin inhibition of the cytotoxic function of human natural killer cells.

Phenyltin (PT) contamination has been reported in water, sediment, and fish. However, the role of PT in weakening human immune function mediated through natural killer (NK) lymphocytes has not been elucidated. In this study, we report the effects of in vitro exposure to triphenyltin (TPT), diphenyltin (DPT), and monophenyltin (MPT) on the function of human NK cells. Exposure to TPT (1 microM, for 1 h) inhibited the tumor killing capacity of NK cells by 85%. Exposure of NK cells to DPT for 1 h (5 microM) and 24h (1.5 microM) reduced tumor lysis by greater than 90%. A 24-h exposure of NK cells to 5 microM MPT reduced tumor lysis by greater than 80%. Assays assessing the ability of NK cells to bind to tumor cells showed that a 24-h pretreatment with TPT, DPT, or MPT reduced NK cell binding to tumor cells by greater than 50%. The toxic potential of the PTs followed the order TPT > DPT > MPT. In comparison with butyltins (BTs), in vitro effects of PTs revealed that these compounds are relatively less toxic to NK cells than BTs. The results of this study provide evidence that phenyltin compounds are immunotoxic to human NK cells under in vitro experimental conditions.

Cell Adhesion↗
PubMed1999

Recurrent and de novo glomerular disease after renal transplantation: a report from Renal Allograft Disease Registry (RADR).

INTRODUCTION: Short-term and long-term results of renal transplantation have improved over the past 15 years. However, there has been no change in the prevalence of recurrent and de novo diseases. A retrospective study was initiated through the Renal Allograft Disease Registry, to evaluate the prevalence and impact of recurrent and de novo diseases after transplantation. MATERIALS AND METHODS: From October 1987 to December 1996, a total of 4913 renal transplants were performed on adults at the Medical College of Wisconsin, University of Cincinnati, University of California at San Francisco, University of Louisville, University of Washington, Seattle, and Washington University School of Medicine. The patients were followed for a minimum of 1 year. A total of 167 (3.4%) cases of recurrent and de novo disease were diagnosed by renal biopsy. These patients were compared with other patients who did not have recurrent and de novo disease (n=4746). There were more men (67.7% vs. 59.8%, P<0.035) and a higher number of re-transplants (17% vs. 11.5%, P<0.005) in the recurrent and de novo disease group. There was no difference in the rate of recurrent and de novo disease according to the transplant type (living related donor vs. cadaver, P=NS). Other demographic findings were not significantly different. Common forms of glomerulonephritis seen were focal segmental glomerulosclerosis (FSGS), 57; immunoglobulin A nephritis, 22; membranoproliferative glomerulonephritis (GN), 18; and membranous nephropathy, 16. Other diagnoses include: diabetic nephropathy, 19; immune complex GN, 12; crescentic GN (vasculitis), 6; hemolytic uremic syndrome-thrombotic thrombocytopenic purpura (HUS/TTP), 8; systemic lupus erythematosus, 3; Anti-glomerular basement membrane disease, 2; oxalosis, 2; and miscellaneous, 2. The diagnosis of recurrent and de novo disease was made after a mean period of 678 days after the transplant. During the follow-up period, there were significantly more graft failures in the recurrent disease group, 55% vs. 25%, P<0.001. The actuarial 1-, 2-, 3-, 4, and 5-year kidney survival rates for patients with recurrent and de novo disease was 86.5%, 78.5%, 65%, 47.7%, and 39.8%. The corresponding survival rates for patients without recurrent and de novo disease were 85.2%, 81.2%, 76.5%, 72%, and 67.6%, respectively (Log-rank test, P<0.0001). The median kidney survival rate for patients with and without recurrent and de novo disease was 1360 vs. 3382 days (P<0.0001). Multivariate analysis using the Cox proportional hazard model for graft failure was performed to identify various risk factors. Cadaveric transplants, prolonged cold ischemia time, elevated panel reactive antibody, and recurrent disease were identified as risk factors for allograft failure. The relative risk (95% confidence interval) for graft failure because of recurrent and de novo disease was 1.9 (1.57-2.40), P<0.0001. The relative risk for graft failure because of posttransplant FSGS was 2.25 (1.6-3.1), P<0.0001, for membranoprolifera. tive glomerulonephritis was 2.37 (1.3-4.2), P<0.003, and for HUS/TTP was 5.36 (2.2-12.9), P<0.0002. There was higher graft failure (64.9%) and shorter half-life (1244 days) in patients with recurrent FSGS. CONCLUSION: In conclusion, recurrent and de novo disease are associated with poorer long-term survival, and the relative risk of allograft loss is double. Significant impact on graft survival was seen with recurrent and de novo FSGS, membranoproliferative glomerulonephritis, and HUS/TTP.

Adult↗
PubMed1999

Primary intracranial neoplasms in patients with HIV.

OBJECTIVE: To report a series of HIV-infected patients with intracranial tumors not known to be associated with immunodeficiency. BACKGROUND: The spectrum of HIV-associated diseases is changing with improved treatments and prolonged patient survival. Although primary central nervous system lymphoma (PCNSL) and toxoplasmosis continue to be the most common intracranial lesions in HIV-infected patients, the recognition of other pathologic entities is increasingly important. METHODS: The clinical characteristics and outcome of eight HIV-infected patients with nine intracranial neoplasms other than PCNSL are reported. In addition, all available pathologic specimens were tested for evidence of either HIV or Epstein-Barr virus (EBV) infection. An additional 28 patients reported in the literature are summarized. RESULTS: Five of eight patients had a glioblastoma multiforme; other tumors included an anaplastic ependymoma, a low-grade glioma, a subependymoma, and a leiomyosarcoma. More than half of the patients developed their tumor > or =6 years after the diagnosis of HIV infection. Patient prognosis and survival was best predicted by tumor histology. Treatment response and outcome did not appear to be influenced by HIV infection. Only the leiomyosarcoma demonstrated evidence of latent EBV infection. CONCLUSIONS: HIV-infected patients are at risk for intracranial neoplasms other than PCNSL, and benefit from aggressive tumor-specific therapy. It is possible that gliomas are occurring at a higher rate than in the general population. There was no evidence of HIV or EBV infection in any glial tumor.

Adult↗
PubMed1999

Pre-transplant identification of risk factors that adversely affect length of stay and charges for renal transplantation.

BACKGROUND: In the current era of renal transplantation, increasing attention is being focused on resource utilization. The purpose of this study was to identify demographic, medical and immunologic risk factors that are associated with changes in length of stay (LOS) and charges for renal transplantation. METHOD: The study was a retrospective analysis of 311 consecutive renal transplants performed at a single institution. Univariate and multivariate analyses were used to examine relationships between risk factors, LOS, charges and post-operative complications. RESULTS: The following pre-transplant variables were found to be independently significant in predicting increased LOS and/or charges: African-American race, obesity for women, chronic obstructive pulmonary disease (COPD), presence of cardiac disease or previous stroke, pre-transplant dialysis time > or = 1 yr, a 10% increase in panel reactive antibody (PRA), cadaver donor and retransplantation. The analyses were performed with and without adjustment for key outcome variables such as delayed graft function (DGF) and use of induction antibody therapy. Increased LOS or charges for specific risk factors could be attributed to increased complication rates, including delayed graft function seen with various co-morbidities, or increased immunologic risk and more frequent use of induction antibody therapy. CONCLUSION: Analysis of linked financial and clinical databases can reveal demographic, medical and immunologic risk factors that correlate with LOS, charges and complications for renal transplantation. Efforts to establish quantitative relationships for various risk factors relative to resource utilization will become important in managed care and/or capitated healthcare delivery systems.

Adult↗
PubMed1999

Renal transplantation for end-stage renal disease following bone marrow transplantation: a report of six cases, with and without immunosuppression.

UNLABELLED: BACKGROUND. Over 12000 bone marrow transplantations (BMT) are performed in the USA each year. This procedure is associated with significant morbidity including acute and chronic renal failure (CRF). CRF after BMT is usually secondary to radiation nephropathy and,or cyclosporine (CsA) toxicity. Survival on dialysis therapy for patients with radiation nephropathy is poor and renal transplantation may be a preferable form of renal-replacement therapy. METHODS: We report our experience with renal transplantation in 6 patients with end-stage renal disease (ESRD) following BMT: 4 as a result of radiation nephropathy; one secondary to hemolytic uremic syndrome; and 1 as a result of antitubular basement membrane nephritis. Ages at the time of BMT ranged from 26 to 40 yr. ESRD developed after a mean period of 94 months (range 42-140 months) after BMT. The kidney source was from a living donor in 5 patients, and a cadaveric donor (CAD) in 1 patient. In 3 recipients, the bone marrow and kidney were from the same donor. They are managed without any immunosuppressive therapy. The other 3 were initiated on triple therapy (prednisone, mycophenolate mofetil/azathioprine and cyclosporine/tacrolimus). RESULTS: These patients have been followed for up to 31 months (range 3-30 months) after kidney transplant, and 5 out of 6 are alive with functioning bone marrow and renal transplants. Their plasma creatinines range from 70 to 160 micromol/L (mean 97 micromol/L). One patient died following metastatic squamous cell cancer of the genital tract. CONCLUSIONS: 1) Renal transplant is a feasible alternative for patients with ESRD following BMT: 2) if bone marrow and kidney are from the same donor, the recipient requires little or no maintenance immunosuppression; 3) short-term results show good survival, but long-term follow-up is needed: 4) infections and malignancy post-renal transplantation were seen in recipients who needed immunosuppression; and 5) reduction in immunosuppression may be needed in such post-BMT patients who undergo kidney transplants.

Adult↗
PubMed1998

Brain abscesses in children with cancer.

BACKGROUND: Brain abscesses in pediatric patients are rare events, and the causative organism and prognosis vary with the population under study. Children with cancer seem to be particularly susceptible to the development of brain abscesses because of the immunological changes induced by cancer and its treatment. We reviewed the records of children who developed a brain abscess during treatment of a malignancy to define the clinical characteristics, prognosis, and management of these patients. PROCEDURE: We performed a retrospective review of the clinical and laboratory characteristics of all cancer patients younger than age 20 years who were admitted to our institution between 1980 and 1996 for a brain abscess. RESULTS: Twelve children were identified. Cancer diagnoses were brain tumor in two, systemic PNET in two, and leukemia in eight. Six patients had multiple abscesses. Eleven received prior chemotherapy. Abscesses were surgically excised or aspirated in seven, and empiric antibiotics were given to the other five. At surgery, Listeria monocytogenes, Aspergillus fumigatus (3), Fusarium, and Candida lusitanea were cultured. Aspergillus was identified in other locations in four patients. Abscesses were successfully treated in seven patients, two of whom received antibiotics only; five patients (42%) died from infection. CONCLUSIONS: Mortality is high in this immunosuppressed population, in part due to the preponderance of fungal infection. The finding of very rare organisms suggests that drainage and culture should be performed whenever possible; empiric antibiotics that include an antifungal agent may, on occasion, be successful.

Abscess↗
PubMed1998

Recurrent and de novo renal diseases after renal transplantation: a report from the renal allograft disease registry.

Recurrent or de novo glomerular disease is an important cause of graft dysfunction and eventual loss. Cyclosporine A (CyA) has improved short-term renal allograft outcome but has not altered long-term graft survival. The purpose of the current study is to determine the prevalence of such disease and its impact on graft function in the CyA era. From 1984 to 1994, 1,557 renal allografts were performed at the Medical College of Wisconsin and the University of Cincinnati. Patients were followed up for an average of 7.2 years (minimum, 1 year). Recurrent disease was diagnosed by renal biopsy in 98 (6.3%) patients after an average of 36 months. Demographic characteristics of patients with and without recurrent disease were similar. Glomerulonephritis was the most common finding, occurring in 73 patients, and included focal segmental glomerulosclerosis (FSGS), 25; IgA nephropathy (IgAN), 11; membranous (MN), 11; proliferative, 11; membranoproliferative glomerulonephritis (MPGN), 10; glomerular basement membrane (anti-GBM), 3; and systemic lupus erythematosus (SLE), two. Diabetic nephropathy was present in 22, hemolytic uremic syndrome (HUS) in two, and oxalosis in one. Graft loss occurred in 60 of 98 (61%) recipients. Half-life of the allograft was diminished in patients with recurrent disease, 2,038 +/- 225 versus 3,135 +/- 385 days, P = 0.002. The actuarial allograft survival at 1, 3, 5, and 8 years posttransplantation with recurrence was 88%, 74%, 57%, and 34%, respectively; and the corresponding graft survival for patients without recurrent disease was 80%, 70%, 64%, and 53%, respectively (P = 0.003). The risk of recurrent disease increased with length of graft survival from 2.8% at 2 years to 9.8% and 18.5% at 5 and 8 years, respectively. We conclude that recurrent disease is a significant problem after renal transplantation and is associated with decreased graft survival.

Actuarial Analysis↗
PubMed1998

Importance of allograft biopsy in renal transplant recipients: correlation between clinical and histological diagnosis.

Renal allograft dysfunction after transplantation may be caused by acute rejection (AR), chronic rejection (CR), cyclosporine (CyA) or tacrolimus (FK) toxicity, and other causes such as recurrence of renal disease. Allograft biopsy is the "gold standard" to establish the correct diagnosis. However, many transplant centers routinely do not consider graft biopsy at the onset of renal dysfunction; instead, empirical steroid therapy or CyA dose reduction is the initial response to graft dysfunction. In this study, we prospectively predicted the histological findings prior to renal biopsy and correlated the clinical and histological diagnoses after the final report was issued by the pathologist. Patients with renal dysfunction after transplantation (increased serum creatinine >20% from baseline) were submitted to allograft biopsy. Three clinicians (C1, C2, and C3) involved in the care of these patients independently predicted the histological findings prior to the biopsy. A total of 100 cases (62 men, 38 women; 71 whites, 29 blacks) with a mean age of 41 years (21 to 70 years) were included in this study. Biopsy samples were taken after a mean period of 1.6 +/- 0.32 years (median, 0.25 years; range, 4 days to 17 years) after transplantation. Two patients with en bloc pediatric kidneys required postbiopsy blood transfusions for self-limiting bleeding; all other patients had no complications. All patients received azathioprine and prednisone; additionally, 74 received CyA and 19 FK. Final histopathologic diagnoses were AR (30), CyA/FK toxicity (36), AR plus CyA/FK toxicity (17), CR (11), recurrent disease (11), and other (6). In 28 cases (28%), the results of the biopsies showed more than one diagnosis. A completely correct diagnosis was predicted by C1, C2, and C3 in 47%, 42%, and 41% (mean, 43%) of the cases, incorrect diagnosis in 25%, 27%, and 25% (mean, 26%) of the cases, and partially correct diagnosis in 28%, 31%, and 34% (mean, 31%) of the cases, respectively. AR was confirmed histologically in 26 of 47 cases (55%) in the presence of therapeutic or high CyA/FK blood levels, whereas in 41 of 53 cases (77%), the histology showed CyA/FK toxicity in the presence of therapeutic or low CyA/FK blood levels. The mean serum creatinine at the time of the biopsy was 2.92 +/- 0.30 mg/dL, compared with the baseline of 1.76 +/- 0.10 mg/dL (P < 0.0001). After appropriate treatment, mean serum creatinine was 2.38 +/- 0.33 mg/dL (P < 0.0001). These data show that clinical prediction was poor, with totally correct diagnosis in only 43% of the cases. In 26%, the diagnosis was incorrect. We conclude that the renal biopsy is essential for establishing the correct diagnosis of renal allograft dysfunction and the appropriate management thereof.

Adult↗
PubMed1997

Risk factors for renal allograft survival from older cadaver donors.

BACKGROUND: The shortage of cadaver donors for kidney transplantation has prompted many centers to use kidneys from older donors. The use of older donor kidneys has been associated with lower graft survival. METHODS: United Network for Organ Sharing data of all adult cadaveric renal transplant recipients receiving kidneys from adult donors between 1988 and 1994 (transplants, n=35,621) were analyzed to further study this issue. All patients were followed for a minimum of 1 year after transplantation. The recipients were classified according to donor age: group 1, 19-50 years; group 2, 51-60 years; and group 3, >60 years. RESULTS: The actuarial kidney survival estimates for group 1: (n=27,999) at 1, 3, and 5 years were 82.7%, 72.2%, and 61.4%. The corresponding values for group 2 (n=5,367) and group 3 (n=2,255) were 77.3%, 63.3%, and 51.3%; and 71.7%, 55.3%, and 42.7%, respectively (P<0.0001). Logistic regression analysis for 1-year graft survival was performed, and odds ratios (ORs) were computed for various risk factors. Increased odds of graft failure were seen with increasing donor age, previous transplantation, and elevated panel-reactive antibody. In the older donor group, lower ORs were observed if the recipients were Hispanic or Asian. In addition, kidneys from African-American or Asian donors had a poorer graft outcome. A similar analysis for 3-year graft survival for those grafts functioning at 1 year revealed poorer survival with older African-American donors (OR=1.78, P<0.02), whereas improved survival rates were seen when older kidneys were used for older (OR=0.635, P<0.01) and female (OR=0.733, P < 0.01) recipients. Statistically significant factors such as HLA mismatch, cold ischemia time, and African-American or diabetic recipients differ in their impact on graft survival across the donor age groups. CONCLUSION: In conclusion, kidneys from older donors are associated with poorer graft survival rates with African-American and Asian donors and African-American recipients, and no detrimental effects when used for older, Hispanic, Asian, or female recipients.

Adult↗