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Basit Javaid

Publications and source records attributed to Basit Javaid.

9 recordsLinked to original sources
PubMed2006

Treatment of renal allograft polyoma BK virus infection with leflunomide.

BACKGROUND: Polyoma BK virus produces an aggressively destructive nephropathy in approximately 3% to 8% of renal allografts, is associated with graft loss within one year in 35% to 67% of those infected and there is no therapy of proven efficacy. Leflunomide is an immune suppressive drug with anti viral activity in vitro and in animals. METHODS: We treated twenty-six patients with biopsy proven NK virus nephropathy (BKN) with either leflunomide alone (n=17) or leflunomide plus a course of cidofovir (n=9) and followed them for six to forty months. Leflunomide was dosed to a targeted blood level of active metabolite, A77 1726, of 50 microg/ml to 100 microg/ml (150 microM to 300 microM). Response to treatment was gauged by serial determinations of viral load in blood and urine (PCR), serum creatinine, and repeat allograft biopsy. RESULTS: In the 22 patients consistently sustaining the targeted blood levels of active drug, blood and urine viral load levels uniformly decreased over time (P<.001). Mean serum creatinine levels stabilized over the first six months of treatment, and with 12 months or more of follow-up in 16 patients the mean serum creatinine has not changed significantly from base line. Four patients who did not consistently have blood levels of active drug (A77 1726) above 40 microg/ml did not clear the virus until these levels were attained or cidofovir was added. CONCLUSIONS: Leflunomide inhibits Polyoma virus replication in vitro and closely monitored leflunomide therapy with specifically targeted blood levels appears to be a safe and effective treatment for Polyoma BK nephropathy.

Aniline Compounds↗
PubMed2005

Implications of immunohistochemical detection of C4d along peritubular capillaries in late acute renal allograft rejection.

BACKGROUND: Immunohistochemical detection of the C4d complement product along peritubular capillaries (PC) may indicate humoral rejection of renal allografts. We examined the frequency of PC C4d expression in renal-allograft biopsies with acute rejection (AR) arising more than 6 months after transplantation and the impact of this finding. METHODS: C4d was detected by immunoperoxidase in 2-micron paraffin sections of consecutive biopsies obtained over a 3-year period. The extent was classified as diffuse (> or =50% PC C4d+), focal (<50% C4d+), and negative (C4d-). Clinical data were obtained by retrospective chart review. Fifty-five AR episodes with Banff 97 types 1A (n = 13), 1B (n = 26), 2A (n = 11), 2B (n = 3), and 3 (n = 2) met inclusion criteria. RESULTS: PC C4d expression was diffuse in 23 (42%), focal in 9 (16%), and negative in 23 (42%) biopsies. AR episodes with focal and diffuse C4d expression had higher proportionate elevation of serum creatinine at biopsy and 4 weeks after diagnosis (P< or =0.05). Biopsies with diffuse PC C4d had interstitial hemorrhage (56.5%) and plasmacytic infiltrates (52%) more frequently than C4d- biopsies (22% and 16%), P = 0.02, but had no other distinctive histologic features. Graft loss was greater in diffuse (65%) compared with focal C4d+ (33%) and C4d- (33%) groups 1 year after diagnosis, P = 0.03. Other clinical and pathologic parameters did not differ significantly, including treatment received for AR. CONCLUSION: Evidence of acute cellular with occult humoral rejection is identified in more than 40% of late AR episodes. Late acute humoral rejection may be associated with interstitial hemorrhage and plasma cells and contributes significantly to graft loss.

Biopsy↗
PubMed2005

Polyoma virus infection of renal allografts: relationships of the distribution of viral infection, tubulointerstitial inflammation, and fibrosis suggesting viral interstitial nephritis in untreated disease.

Whether polyoma virus (PV) infection of renal allografts induces an antiviral or antigraft immune reaction is unclear. By examination of the relationships of tubular PV to graft inflammation and scarring, this study sought histological evidence of viral interstitial nephritis in allograft biopsies with untreated PV infection and compared the inflammatory indices to controls with acute rejection (AR). Morphological features including viral cytopathic changes (VCCs) and modified Banff 97 histological indices were evaluated in sections of 28 diagnostic biopsies from a group of patients receiving prednisone, tacrolimus, and mycophenolate mofetil at constant dosage before biopsy. Two-micrometer paraffin sections were stained for PV large T antigen (TAg) and for C4d, by immunohistochemistry. Tubular profiles with 1 or more nuclei expressing TAg per x200 field were scored using an interval scale (0-10; none to 91-100%) by 2 observers. Controls with AR (n = 38, TAg negative) were matched for time after transplantation and severity of Banff 97 interstitial inflammation (i) and tubulitis (t) scores. Median t scores for tubules with VCC or TAg or both exceeded scores for tubules without VCC or TAg (3 versus 0, P = .001). Tubular TAg score correlated with i score (r = 0.58, P < .01) and sum ct + ci score (r = 0.61, P < .001). Atrophic tubules in scars had persistent VCC and/or TAg. Interstitial plasma cells (75% versus 21%) and neutrophils (32% versus 0%) were more frequent, and interstitial fibrosis was more severe (ci >1 in 54% versus 21%) in polyoma virus nephropathy (PVN) than in the group with AR (P < .01). Intimal arteritis (0% versus 35.7%), peritubular capillary C4d (0% versus 47.4%), and interstitial hemorrhage (4% versus 37%) were almost exclusively found in AR (P < .01). Tubular inflammation in untreated PVN involves infected tubular profiles with greater severity than those without evidence of infection. The extent of tubular PV infection is proportional to interstitial inflammation and scarring. Tubulointerstitial inflammation in PV infection has significant qualitative differences from AR. Observations in these examples of untreated PVN suggest that the allograft inflammatory reaction may exhibit features of viral tubulointerstitial nephritis distinct from AR.

Biopsy↗
PubMed2005

Treatment of glomerulonephritis: will we ever have options other than steroids and cytotoxics?

Glomerulonephritis refers to a collection of primary renal disorders and those secondary to a systemic disease, all characterized by inflammation within the glomerulus. Given the underlying immunologic nature of these disorders, they are routinely treated with corticosteriods and various cytotoxic agents. Although in many instances such therapies are successful, they are associated with significant morbidity; as such, alternatives are clearly necessary. Our understanding of the pathogenesis of immunologic glomerular diseases has grown remarkably, in large part from the study of rodent disease models. Fundamental to each disorder is the development of an antigen-specific immune response followed by the effector stage of inflammation. To block the immune response, antigen-specific therapy can be used to induce tolerance, such as through the use of double-stranded DNA molecules in lupus nephritis. Since other antigen systems are less well characterized, inducing a more generalized impairment in the immune response by blocking costimulatory molecules CD40-CD154 and CD28-CD80/86 is a growing approach to treat various immunologic disorders and transplantation. To reduce glomerular inflammation, a variety of effector systems have been targeted, including complement, cytokines/chemokines, adhesion molecules, and mediators of cellular proliferation. Of these, antibodies targeting C5 in the complement system, and antibody and receptor antagonists of tumor necrosis factor-alpha (TNF-alpha) have already been used in glomerular disorders with some promise. Less specific blockade of receptor-mediated events stimulated by platelet-derived growth factors and cell cycle proteins may soon be applied to glomerulonephritis. Finally, interruption of fibrosing pathways, which lead to glomerulosclerosis and interstitial fibrosis common to the end-stage of all glomerulonephritis, is the subject of intense effort which may yield effective biologic therapies. In spite of all these advances, we still are dependent on steroids and cytotoxics to treat glomerulonephritis. To get past this, we must devote significant resources to take observations made in basic research laboratories to develop therapeutics and prove their utility in human disease.

Adrenal Cortex Hormones↗
PubMed2004

Cardiovascular diseases in kidney transplant recipients: the role of anemia.

Cardiovascular diseases are among the leading causes of mortality and death associated graft loss in kidney transplant recipients. Recently, there has been an increased awareness of the potential role of nontraditional risk factors such as anemia in contributing to the increased burden of cardiovascular diseases in kidney transplant recipients. Studies that are primarily based on retrospective data analyses have shown an association between anemia and cardiovascular outcomes. These findings underscore the need for prospective studies to better understand these risks and to implement management strategies that would have a positive impact on patient and graft outcomes. On the basis of the available data, this article reviews the magnitude of cardiovascular diseases and anemia in kidney transplant recipients with a focus on the role of anemia on cardiovascular outcomes in these patients.

Anemia↗
PubMed2003

Treatment of de novo and recurrent membranous nephropathy in renal transplant patients.

Membranous nephropathy (MN) is one of the common glomerular diseases diagnosed in transplanted kidneys. The exact impact of posttransplantation MN on the risk for graft loss and long-term graft outcome is not defined clearly. In recent reports, it has emerged as the third most frequent glomerulonephritis (de novo or recurrent) associated with renal allograft loss. Most cases of posttransplantation MN are thought to be idiopathic but cases associated with established secondary causes also have been reported. Patients can present with varying degrees of proteinuria and graft dysfunction. Risk factors that predict a poor outcome are not well established and unlike MN in the native kidneys, spontaneous remission is rare. Patients should be evaluated carefully for complications associated with nephrotic syndrome or graft dysfunction and managed accordingly. The beneficial effects of steroids, cyclosporine, mycophenolate mofetil, cyclophosphamide, chlorambucil, or other agents have not been validated. The role of specific treatments in cases of secondary MN is uncertain. Retransplantation is a reasonable option for patients who develop graft failure secondary to MN.

Clinical Trials as Topic↗
PubMed2001

Glomerular injury and tubular loss in adriamycin nephrosis.

Glomerular injury manifested by sustained proteinuria usually leads to tubule injury and reduction of the GFR. The current study explored the link between these processes in rats with adriamycin nephrosis. One group of nephrotic rats received a vasopressin V2 receptor blocker (V2X) from 4 to 16 wk after injection of adriamycin, whereas a second group received no treatment (NoRx). V2 receptor blockade increased urine volume without affecting protein excretion. At 16 wk, both groups of nephrotic rats exhibited a marked reduction in GFR in comparison with normal controls (V2X, 0.22 +/- 0.19 ml/min; NoRx, 0.20 +/- 0.11 ml/min; control, 1.23 +/- 0.11 ml/min). Morphologic studies revealed that the majority of glomeruli in nephrotic rats were no longer connected to normal tubule segments (V2X, 81 +/- 21%; NoRx, 85 +/- 18%; control, 1 +/- 2%). Glomeruli without tubules were not, however, globally sclerosed. Disruption of the glomerular tubular junction was associated with the presence of amorphous material separating damaged tubule cells from the basement membrane. Serial sections revealed that this material spread from extensive areas of adhesion between the glomerular tuft and capsule to invest the tubular neck. Reduction of the GFR was strongly correlated with the fraction of glomeruli not connected to normal tubules (r(2) = 0.82; P < 0.0001). V2 receptor blockade did not preserve renal function or structure. These findings suggest that local extension of glomerular injury to destroy the tubule neck is an important cause of loss of renal function in adriamycin nephrosis.

Animals↗