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Titte R Srinivas

Publications and source records attributed to Titte R Srinivas.

8 recordsLinked to original sources
PubMed2004

Macrophage index predicts short-term renal allograft function and graft survival.

The ability to predict renal allograft dysfunction in the short term and predict graft survival by quantifying the macrophage infiltrate in allograft renal biopsies is described. Renal allograft biopsies performed for cause in 41 consecutive patients were scored for macrophages (macrophage index, MI) by use of a modified Banff score of inflammation (BSI), and the impact of the MI on serum creatinine (SCr) levels 3 months post-biopsy (post-Bx) and on graft survival was quantified. Biopsies were stained for macrophages, individual lesions semiquantified and MI, BSI and chronic allograft damage index (CADI) obtained. The effects of pathologic indices on 3 month post-Bx SCr and graft survival were quantified by multivariate analysis and Cox regression. Glomerular and interstitial macrophage scores correlated inversely with graft survival. MI predicted an increase in SCr 3 months post-Bx (P=0.02). MI >3 (hazard ratio 23.13, P=0.003) also had a powerful negative predictive value on graft survival.

Biomarkers↗
PubMed2004

Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era.

Acute rejection is known to have a strong impact on graft survival. Many studies suggest that very low acute rejection rates can be achieved with current immunosuppressive protocols. We wanted to investigate how acute rejection rates have evolved on a national level in the U.S. and how this has impacted graft survival in the most recent era of kidney transplantation. For this purpose, we analyzed data provided by the Scientific Registry of Transplant Recipients regarding all adult first renal transplants between 1995 and 2000. We noted a significant decrease in overall acute rejection rates during the first 6 months, during the first year, and also in late rejections during the second year after transplantation. Despite this decrease in the rate of acute rejection, there was no significant improvement in overall graft survival; furthermore, we noted a statistically significant trend towards worse death-censored graft survival. There was also a trend for a greater proportion of rejection episodes to fail to recover to previous baseline function after treatment. Our data suggest that decreasing acute rejection rates between 1995 and 2000 have not led to an increase in long-term graft survival. Part of this discordance might be related to a higher proportion of acute rejections which have not resolved with full functional recovery in more recent years. However, the etiology of this concerning trend for worse death censored graft survival in recent years will warrant further investigation.

Graft Rejection↗
PubMed2004

Kidney transplantation halts cardiovascular disease progression in patients with end-stage renal disease.

Morbidity and mortality from cardiovascular disease have a devastating impact on patients with chronic kidney disease (CKD) and end-stage renal disease. Renal function decline in itself is thought to be a strong risk factor for cardiovascular disease (CVD). In this study, we investigated the hypothesis that the elevated CV mortality in kidney transplant patients is due to the preexisting CVD burden and that restoring renal function by a kidney transplant might over time lower the risk for CVD. We analyzed 60,141 first-kidney-transplant patients registered in the USRDS from 1995 to 2000 for the primary endpoint of cardiac death by transplant vintage and compared these rates to all 66813 adult kidney wait listed patients by wait listing vintage, covering the same time period. The CVD rates peaked during the first 3 months following transplantation and decreased subsequently by transplant vintage when censoring for transplant loss. This trend could be shown in living and deceased donor transplants and even in patients with end-stage renal disease secondary to diabetes. In contrast, the CVD rates on the transplant waiting list increased sharply and progressively by wait listing vintage. Despite the many mechanisms that may be in play, the enduring theme underlying rapid progression of atherosclerosis and cardiovascular disease in renal failure is the loss of renal function. The data presented in this paper thus suggest that the development or progression of these lesions could be ameliorated by restoring renal function with a transplant.

Adolescent↗
PubMed2003

Mycophenolate mofetil in solid-organ transplantation.

This review focuses on the use of mycophenolate mofetil (MMF) as an immunosuppressive agent in solid-organ transplantation. MMF, a non-competitive inhibitor of inosine monophosphate dehydrogenase, blocks de novo purine synthesis in T and B lymphocytes, resulting in the selective inhibition of proliferation of these cells in response to antigenic stimuli. MMF may also promote apoptosis of these cells. The immunosuppressive ability of MMF is thought to derive mainly from the inhibition of inosine monophosphate dehydrogenase. The other effects of MMF include suppression of antibody synthesis by B lymphocytes, inhibition of proliferation of smooth muscle cells in culture and impaired glycosylation of adhesion molecules. MMF may exhibit anti-inflammatory effects resulting from decreased activity of the inducible form of nitric oxide synthase, a consequence of depletion of tetrahydrobiopterin, which leads to decreased generation of peroxynitrite, a pro-inflammatory molecule. The pharmacokinetics, pharmacodynamics and principles underlying therapeutic drug monitoring of MMF are reviewed. The results of the pivotal clinical trials of MMF in kidney and heart transplantation are discussed and a summary of the major studies demonstrating a positive effect of MMF on renal transplantation outcomes is presented. The use of MMF in the context of ABO-incompatible renal transplantation, renal transplantation in highly sensitised and cross-match positive recipients, humoral rejection of renal allografts, chronic allograft nephropathy and steroid/calcineurin inhibitor minimisation in renal transplantation are also discussed.

Animals↗
PubMed2002

The changing causes of graft loss and death after kidney transplantation.

BACKGROUND: The results of kidney transplantation have improved markedly over the last three decades. Despite this, patients still lose grafts and die. We sought to determine whether the causes of graft loss and death have changed over the last 30 years. METHODS: We reviewed patients who underwent transplantation or who died between January 1, 1970 and December 31, 1999. We compared the causes of graft loss or death for three decades: 1970 to 1979, 1980 to 1989, and 1990 to 1999. RESULTS: From January 1, 1970 to December 31, 1999, we performed 2501 kidney transplantations in 2225 patients. For the three periods, 210, 588, and 383 patients lost their grafts, respectively. Graft survival increased substantially. Graft loss occurred later after transplantation, with 36.0% losing grafts in the first year during 1970 to 1970, 22.8% during 1980 to 1989, and 11.4% during 1990 to 1999. Death with a functioning graft increased from 23.8% for 1970 to 1979 to 37.5% for 1990 to 1999. Concomitantly, rejection as a cause of graft loss fell from 65.7% for 1970 to 1979 to 44.6% for 1990 to 1999. Approximately two thirds of the patients who died after transplantation died with a functioning graft and one third died after returning to dialysis. Cardiac disease as a cause of death increased from 9.6% for 1970 to 1979 to 30.3% for 1990 to 1999. Deaths from cancer and stroke also increased significantly over the three decades from 1.2% and 2.4%, respectively, for 1970 to 1979, to 13.2% and 8.0%, respectively, for 1990 to 1999. CONCLUSIONS: The causes of graft loss and death have changed over the last three decades. By better addressing the main causes of death, cardiac disease, and stroke with better prevention, graft loss due to death with a functioning graft will be reduced.

Adolescent↗
PubMed2002

Factors associated with long-term renal allograft survival.

Major advances in immunosuppression and reductions in the rates of acute rejection have led to increasing graft and patient survival rates during the past two decades. Chronic dysfunction of the renal allograft, however, remains a major clinical problem and probably represents the end result of the complex interplay between donor and recipient factors, immunologic injury, nonimmunologic insults, and drug-induced nephrotoxicity. Optimal function of the renal allograft is obtained by maintaining a balance between underimmunosuppression and acute rejection and overimmunosuppression and drug-induced toxicities. To minimize side effects while maintaining efficacy, immunosuppressive drugs are commonly used as combination therapy. Pharmacokinetic and pharmacodynamic interactions between these agents can affect graft survival and function. The evidence supporting the role of therapeutic drug monitoring as applied to commonly used immunosuppressants in modern transplantation is presented here, and the increasing role of therapeutic drug monitoring in the optimization of graft and patient survival rates in the modern era of renal transplantation is discussed.

Drug Monitoring↗