A Single-center Experience of Kidney Transplantation from Donation after Circulatory Death: Challenges and Scope in India.

Donation after circulatory death (DCD) has never been attempted in India because of legal constraints and lack of guidelines for the withdrawal of life support in end-of-life situations. The present report describes the initial experience of transplantation of organs from DCD donors in a tertiary care center in India. Between 2011 and 2015, five donors had kidneys retrieved after cardiac arrest. These patients were declared dead after waiting for 5 min with no electrocardiographic signal on monitor following cardiopulmonary resuscitation (CPR), which was restarted in three patients till organ retrieval. All donors received heparin and underwent rapid cannulation of aorta, infusion of preservative cold solution, and immediate surface cooling of organs during retrieval surgery. 9/10 kidneys were utilized. Mean donor age was 29.6 ± 16.3 years, M:F 4:1 and mean age of recipients was 38.7 ± 10.8 years, M:F 7:2. Seven patients required dialysis in postoperative period. Mean postoperative day 0 urine output was 1.9 ± 2.6 L. Baseline creatinine achieved was 1.38 ± 0.35 mg/dl after a mean duration of 26.12 ± 15.4 days. Kidneys from donors where CPR was continued after the declaration of death (n = 3) had better recovery of renal function (time to reach baseline creatinine 21.2 ± 7.2 vs. 34.3 ± 23.7 days, baseline creatinine 1.36 ± 0.25 vs. 1.52 ± 0.45 mg%). In donors without CPR, one kidney never functioned and others had patchy cortical necrosis on protocol biopsy, which was not seen in the kidneys from donors with CPR. Kidneys from DCD donors can serve as a useful adjunct in deceased donor program. Continuing CPR after the declaration of death seems to help in improving outcomes.

Outcomes of spousal versus related donor kidney transplants: A comparative study.

This study was designed to compare the outcomes of spousal donor (SD) with related donor (RD) kidney transplants performed at our center between January 2010 and October 2012. A total of 323 adult, ABO-compatible kidney transplants (SD 150 [46.4%], RD 173 [53.6%]) were included. Data on outcomes at 6 months post-transplant was collected retrospectively (2010-2011) and prospectively (January-October 2012). Majority of the donors (SD 88%, RD 72.2%) were females. In the SD group, donors were younger (SD 35.6 ± 8.2 years, RD 45.2 ± 11.5 years; P < 0.0001), whereas recipients were older (SD 42.2 ± 8.3 years, RD 30.0 ± 9.5 years; P < 0.0001). A significantly higher proportion of patients in the SD group were given induction therapy (43% vs 12%; P < 0.001). Biopsy proven acute rejections were more common in the RD group (16% vs 28.3%; P = 0.01). Majority (80.8%) of the acute rejections occurred in the first 2 weeks post-transplant in both groups. Isolated acute cellular rejections (ACRs) and isolated antibody mediated rejections constituted 50% and 25% of rejection episodes in both groups, whereas the remainder had histological evidence of both. The proportion of steroid responsive ACRs was similar in both groups (SD 83.3%, RD 65.4%; P = 0.2). The number of patients with abnormal graft function at the end of the study was higher in the RD group (2.3% vs. 12.3%; P = 0.001). Patient survival and infection rates were similar in the two groups. We conclude that short-term outcomes of SD transplants are not inferior to RD transplants. Lesser use of induction therapy in the RD group may explain the poorer outcomes as compared to the SD group.

Efficacy of basiliximab induction in poorly matched living donor renal transplantation.

Non-depleting antibody induction has the best safety profile in transplant recipients without an increased risk of infection or malignancy. This observational study was performed in intermediate immunologic risk live donor renal transplants to assess basiliximab efficacy in patients on tacrolimus, mycophenolate, and prednisolone immunosuppression. A total of 46 patients on basiliximab induction were compared to risk matched 56 controls at the end of 6 and 12 months post-transplant. An additional cost of approximately Rs. 100,000/patient was incurred by the basiliximab group. The incidence of biopsy proven acute rejection in the control group (12.5%, 6 months and 20.5%, 1 year) and the basiliximab group (13%, 6 months and 18.9%, 1 year) was similar. At 6 months, there was a non-significant trend toward more steroid sensitive rejections and better glomerular filtration rate preservation in the basiliximab group (83.3%, 71.9 ml/min) versus the control group (28.6%, 62.2 ml/min). However, this difference was lost at 1 year (70.1 ml/min vs. 67.6 ml/min). The incidence of infections was similar and none of the patients had a malignancy. Death censored graft survival (94.6% basiliximab and 94.8% control) and the mean number of hospitalizations for all reasons at the end of 1 year were not different among the two groups. In our study, basiliximab induction did not confer an additional advantage in the intermediate risk live donor transplants in patients on tacrolimus and mycophenolate based triple drug immunosuppression.

Spectrum of lymphoproliferative disorders following renal transplantation in North India.

Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized, but uncommon complication of organ transplantation. This study was a retrospective analysis of 2000 patients who underwent renal transplantation over a period of 30 years (1980-2010). Forty malignancies were diagnosed in 36 patients. Of these, 29 patients (1.45%) had PTLD (7 females, 22 males) accounting for 72.5% of all malignancies after transplantation. Twenty-two (75.8%) developed non-Hodgkin lymphoma and seven patients (24.2%) had myeloma. Diagnosis was made by biopsy of the involved organ in 21 patients (72.4%) and aspiration cytology in five patients (17.2%). In three patients, the diagnosis was made only at autopsy. Mean age at the time of diagnosis of PTLD was 41.9 years (range 21-69 years). Time interval from transplantation to the diagnosis of PTLD ranged from 3 months to 144 months with a median of 48 months. Only five patients (17.2%) developed PTLD within a year of transplantation. Twelve patients developed PTLD 1-5 years and 12 patients 5-10 years after transplantation. Organ involvement was extra nodal in 18 patients (82%). Thirteen (59%) patients had disseminated disease and nine (41%) had localized involvement of a single organ (brain-3, liver-1, allograft-1, perigraft node-1, retroperitoneal lymph nodes-3). Infiltration of the graft was noted in two patients. Patients with myeloma presented with backache, pathological fracture, unexplained anemia or graft dysfunction. PTLD was of B cell origin in 20 cases (70%). CD 20 staining was performed in 10 recent cases, of which 8 stained positive. Of the 26 patients diagnosed during life, 20 (69%) died within 1 year of diagnosis despite therapy. In conclusion, PTLD is encountered late after renal transplantation in the majority of our patients and is associated with a dismal outcome. The late onset in the majority of patients suggests that it is unlikely to be Epstein Barr virus related.

Light chain deposition disease in a postrenal transplant patient.

The morphological spectrum of light chain deposition disease (LCDD) may range from normal glomerular morphology to mesangio-proliferative to mesangio-capillary to nodular sclerosing patterns. Due to the inconsistencies regarding treatment and the universally poor graft outcome of post-transplant LCDD, it is imperative to maintain a high index of suspicion and perform relevant investigations for clinching this diagnosis. A 40-year-old lady was diagnosed as a case of membrano-proliferative glomerulonephritis 3 years back, for which she underwent a live unrelated renal allograft transplant. Postoperative period was complicated by an acute rise in serum creatinine on the 21(st) postoperative day. Biopsy showed patchy acute cortical necrosis, which responded to conservative management. The present admission was for renal failure and subnephrotic proteinuria. A kidney biopsy was performed, and all the 14 glomeruli examined showed a mesangiocapillary pattern of glomerular injury with cellular nodule formation in some. The nodules were PAS and Congo red negative. Immunofluorescence showed glomerular and tubular basement staining for Kappa light chains only. Electron microscopy showed the characteristic granular deposits in subendothelial location in the glomerulus, and in tubular basement membranes, thus confirming the diagnosis of LCDD. Membranoproliferative pattern of glomerular injury in the pre- and posttransplant setting has a wide range of differential diagnoses; LCDD being one of them.

Spectrum of cytomegalovirus-induced renal pathology in renal allograft recipients.

Viral infections in renal allograft recipients constitute an important cause of renal graft dysfunction. They have shown an increasing incidence coinciding with more potent immunosuppression regimens. Cytomegalovirus (CMV) is well-known cause of a tubulointerstitial nephritis rich in plasma cells with cytopathic changes in tubular epithelial and endothelial cells. However, involvement of glomeruli and larger arteries in the absence of tubulointerstitial disease is rare. In this study, we demonstrated the spectrum of renal disease caused by CMV among renal allograft recipients. Retrospective analysis of 2900 renal allograft biopsies performed over a 10-year period revealed 10 cases of CMV infection, with half of them (5/10) detected in 2010-2011. Although tubulointerstitial nephritis due to CMV was the most common lesion (7/10), we noted an increased incidence of CMV glomerulopathy with (1/10) or without (3/10) coexisting tubulointerstitial CMV disease. Isolated glomerular involvement was characterized by a relative lack of inflammation in any of the compartments along with the presence of cytopathic changes in the glomerular endothelial cells and podocytes. Another patient had CMV-induced thrombotic microangiopathy. The coexistent diseases were calcineurin inhibitor toxicity (n = 1), antibody-mediated rejection (n = 1), cellular rejection (n = 2), and invasive fungal infection (n = 1). In conclusion, there is a wide spectrum of CMV-induced lesions. CMV glomerulopathy is characterized by cytopathic changes in glomerular endothelial cells and podocytes with a lack of significant inflammation. In contrast, CMV-induced arteriopathy can present as thrombotic microangiopathy. Coinfection with other pathogens like invasive fungi can lead to graft failure.

Dual positivity of donor and recipient plasma for BK virus confers a high risk for development of bk nephropathy in renal allograft.

BACKGROUND: BK nephropathy (BKN) is an important complication of renal transplantation, with a reported incidence between 1% and 10% in different parts of the world. Known risk factors for the development of BKN are the recently introduced immunosuppressants and steroids. However, the preexisting viral load may add to the risk for development of BKN. Therefore, the present study was designed to monitor the baseline BK virus (BKV) DNA in renal transplant donors and recipients in India for correlation with the development of BKN. METHODS: This study used real-time polymerase chain reaction (PCR) for quantification of BKV DNA in the plasma of kidney transplant donors (n = 38) and recipients (n = 87) at the time of surgery. The control BKV DNA was manufactured from a known positive human sample, by cloning a 133-bp PCR product of bases 4,329 to 4,462 of the large T-antigen (TAg) of BKV in a plasmid vector. RESULTS: Twenty-five of 87 recipient (28.7%) and 17/38 donor (44.7%) plasma samples were positive for BKV DNA at the time of transplantation with a median viral load of 910 (range 49-4770) and 312 (range 79-1508) copies per mL plasma, respectively. Six of 38 donor-recipient pairs showed viremia in both the recipient and donor: 1 developed histologically proven BKN at 18 months, 1 showed positive immunohistochemistry for SV40 TAg, and 2 others had high levels of viremia (14,545 copies at 6 and 2,617,524 copies at 3 months). None of the other 81 recipients showed evidence of BKN in the follow-up period. CONCLUSIONS: This study showed that 28% of recipients and 44% of donors displayed baseline positivity for BKV DNA in plasma, which is higher than the reported incidence in the West. The baseline levels of BKV DNA in recipients with end-stage renal disease were higher than in donors. Dual positivity for BKV DNA in the plasma of donor-recipient pairs conferred a high risk of development of BK nephropathy in the allografted kidney.

Prospective monitoring of BK virus reactivation in renal transplant recipients in North India.

BACKGROUND: BK nephropathy (BKN) is an important complication of renal transplantation with a reported incidence between 1% and 10% in different parts of the world. Early diagnosis is important to plan early therapeutic strategies. The epidemiology and evolution of BKN is relatively unknown in India and hence, the present study has been designed to prospectively monitor the activation of BK virus (BKV) in renal transplant recipients in India. PATIENTS AND METHODS: In this study, 32 renal allograft recipients were prospectively monitored with protocol biopsies of allografts, BKV DNA load in plasma, and viral particles in urine by electron microscopy (EM) on day 1, and at 1, 3, and 6 months. Additionally, the baseline BKV DNA load in plasma was quantitated in 21 corresponding donors. RESULTS: On follow-up in 32 recipients, 9.7%, 23.8%, 19.2%, and 13.3% of patients showed viral profiles by EM at day 1, 1 month, 3 months, and 6 months, respectively. BKV DNA positivity in plasma was 25.8%, 42.9%, 15.4%, and 20% at day 1, 1 month, 3 months, and 6 months, respectively, with mean BKV copy number/mL plasma of 1796, 1029, 2611, and 3318, respectively. A total of 15.7% (17/108) urine samples of 32 renal recipients were positive by urine EM. Out of 100 protocol biopsies, none developed histologically demonstrable cytopathic effects of BKN, although 8% biopsies were SV-40 large T antigen (SV-40 T Ag) positive. By quantitative real-time polymerase chain reaction assay, 27/108 (25%) of recipients' plasma samples were positive for BKV. Peak viremia and viruria occurred at 1-3 months post transplantation. The baseline viremia in donors was predictive of viremia positivity in the post-transplantation period at 1 month. Twenty-four episodes of graft dysfunction were attributed mainly to rejection. CONCLUSION: The study shows a total of 15.7% and 25% urine and plasma samples were positive for BKV at any time during a 6-month follow-up. The highest incidence of BK viruria and viremia occurred at 1 month. In protocol biopsies, focal positivity of SV-40 T Ag was seen in 8% biopsies.

Serial measurements of hepatitis C viral load by real-time polymerase chain reaction among recipients of living-donor renal transplants: a short-term follow-up study from a single center.

There is a high prevalence of hepatitis C virus (HCV) infection among immunosuppressed patients including renal transplant recipients. The study investigated serum viral loads for up to 6 months posttransplantation among these patients. Serum viral load was serially monitored using real-time polymerase chain reaction (PCR) in 25 HCV-positive renal transplant recipients pretransplantation as well as day 10 and 6 months posttransplantation. A liver biopsy specimen obtained under vision at the time of transplantation was analyzed for viral load as well as for histological changes. There was increased viremia at day 10 followed by a significant (2 log) reduction at 6 months posttransplantation. Pretransplantation serum and intrahepatic viral load showed significant positive correlations (r = 0.727; P = .001), the latter also reflecting liver fibrosis score (r = 0.423; P = .05). The findings suggested that serum viral load reflects intrahepatic viral load, which in turn correlates with liver fibrosis. At 6 months posttransplantation, the modulatory effects of immunosuppressive drugs and of the host immune response may lead to a reduced viral load.

An acetazolamide based multimodal analgesic approach versus conventional pain management in patients undergoing laparoscopic living donor nephrectomy.

SUMMARY: Choice of an appropriate anaesthetic technique and adequate pain relief during laparoscopic living donor nephrectomy (LDN) is likely to make the procedure more appealing to kidney donors. Various analgesic regimens proposed to relieve pain after laparoscopic surgery include: opioids, non-opioid analgesics followed by opioids for the breakthrough pain and intra-peritoneal normal saline irrigation and instillation of local anaesthetics at surgical sites. Thorough literature review and medline search did not reveal any study where a combination of orogastric acetazolamide along with intraperitoneal saline irrigation and bupivacaine instillation techniques have been tried in these patients. In a prospective, double blind, randomized trial, eighty healthy adults undergoing LDN under general anaesthesia were enrolled to compare the efficacy of an acetazolamide based multimodal analgesic approach (Group A) with conventional pain management (Group B). Donors' demographics, intra-operative variables, early allograft function and recovery characteristics were evaluated for 72 hours. The primary end points were postoperative pain intensity on a visual analog scale and the incidence of shoulder tip pain (STP). The secondary end points included the latency of the rescue analgesia request rate, total analgesic consumption and patient satisfaction. Consistently lower mean pain scores were observed in Group A (p<0.03 for visceral pain). Frequency as well as the total dose of rescue analgesics administered was significantly less in Group A (p=0.001). Twelve patients (30.7%) in Group B complained of STP compared to three (7.5%) in Group A (p=0.025). Shoulder pain also presented earlier (8 hours versus 12 hours) and persisted for longer period in Group B (72 hours versus 48 hours, p 0.025). To conclude, a multimodal analgesic approach consisting a combination of orogastric acetazolamide, intraperito-neal saline irrigation and use of bupivacaine in the operated renal fossa, pfannenstiel incision and laparoscopic port sites provide significant reduction in postoperative pain after LDN.

Impact of anti-hepatitis C virus (HCV) antibody on outcomes in renal transplant recipients infected with HCV.

OBJECTIVE: Hepatitis C virus (HCV) infection remains an important risk factor for mortality and morbidity in transplant recipients. In this study, we retrospectively analyzed the impact of pretransplantation hepatitis C antibody status in HCV-infected renal allograft recipients on graft and patient survivals. PATIENTS AND METHODS: From February 1998 to August 2007, 933 renal transplantations were performed at our center. Of these, 104 patients were identified to be harboring HCV infection: 59 (group I) were anti-HCV positive prior to transplantation and 45 (group II) were HCV RNA/antibody positive in the posttransplantation period. The patients transplanted in different eras received different immunosuppressive regimens. Complete follow-up data were available for 72.3% (43/59) in group I and 80% (36/45) in group II. Both groups had a similar number of patients on cyclosporine (62.8% vs 61.1%), tacrolimus (37.2% vs 38.8%), and mycophenolate mofetil (MMF; 58.1% vs 61.1%). These patients were analyzed for differences in patient and graft survivals by log-rank test. RESULTS: The overall mean ages were 35.1 +/- 10.4 and 32.4 +/- 10.4 years, male to female ratios 37:6 and 31:5, mean donor ages 41.5 +/- 10.9 and 41.2 +/- 13.1 years, and mean follow-up durations 29.4 +/- 24 (range, 1-107.7) and 32.6 +/- 24.2 (range, 3.1-97.2) months in groups I and II, respectively. The patients in group I had received a significantly greater number of blood transfusions compared with patients in group II (6.2 +/- 5.7 vs 2.1 +/- 2.9) and a significantly greater number of dialysis treatments prior to transplantation (84.5 +/- 62.0 vs 33.8 +/- 43.2), respectively. Liver function tests--SGOT (22.6 +/- 16.1 vs 18.3 +/- 12.1 IU/L) and SGPT (24.2 +/- 28.9 vs 20.4 +/- 20.2 IU/L)-were similar in the 2 groups in the pretransplantation period, respectively. The patient and graft survivals at 5 years were similar: 88.6% vs 82.3% (P = .81) and 60.1% vs 62.5% (P = .75) in groups I and II, respectively. The serum creatinine values at last follow-up were 1.38 +/- 0.6 vs 1.7 +/- 2.4 mg% (P = not significant), SGOT 33.4 +/- 25.6 vs 38.3 +/- 47 IU/L, and SGPT 39.3 +/- 46.7 vs 59.2 +/- 89 IU/L in groups I and II, respectively. Liver decompensation occurred in 4 patients, 2 in each group at a mean duration of 36.5 months. CONCLUSION: Absence of HCV antibody does not confer any survival disadvantage in HCV-infected renal allograft recipients undergoing renal transplantation.

Incidence of glucose metabolic abnormalities in Indian living renal allograft recipients on tacrolimus-based triple drug immunosuppression.

OBJECTIVE: The prevalence of glucose metabolic abnormalities (GMA) and overt diabetes in the Indian population is higher than the Western population. Tacrolimus (generic form), which is known to cause GMA, was recently introduced in India and data on its use in India are scarce. Herein we have presented our experience of the use of tacrolimus in renal transplantation. PATIENTS AND METHODS: We performed a retrospective analysis of 122 consecutive patients receiving tacrolimus-based triple drug immunosuppression at a single center. Target levels were 10 to 15 ng/mL in the first month, 8 to 10 ng/mL in the second to third months, and 5 to 8 ng/mL thereafter. GMA was defined as fasting blood sugar >110 mg% or postprandial blood sugar >140 on more than one occasion. All episodes of graft dysfunction were evaluated by graft biopsy. In addition, all consenting patients underwent protocol biopsy at 1, 3, and 6 months. Overall mean age of recipients was 34.5 +/- 10.1 years; male to female ratio 108:14; mean donor age 40.1 +/- 10.1 years; and mean follow-up 16.8 +/- 5.9 months. RESULTS: The patient and graft survivals at 18 months were 96.7% and 94.8%, respectively. Incidence of clinical biopsy-proven acute rejection was 5.7%. In addition, 8.13% patients had subclinical rejection. The mean serum creatinine at last follow-up was 1.3 +/- 0.6 mg%. Of the nondiabetic recipients, 54.5% developed GMA and 32.7% required drug therapy for glycemic control, of which only 5.5% were insulin dependent. The prevalence of hepatitis C virus (HCV) infection was 20.0% in the cohort. CONCLUSION: Use of tacrolimus results in a low incidence of clinical acute rejection but a high incidence of GMA in Indian transplant recipients.

[Screening for Y chromosome microdeletions in assisted reproductive techniques]. / Recherche des microdélétions du chromosome Y en Assistance médicale à la procréation.

In case of infertility due to azoospermia, clinical, sonographical and biological examinations suggest obstructive or non obstructive causes. In cases of non obstructive azoospermia, genomic microdeletions must be determined particularly in the Y chromosome long arm, as well as autosomal abnormality. A constitutional karyotype must also be done. The so-called Y AZFa, AZFb and AZFc zones could be partially or totally absent. Genotype is mostly correlated with histology. Thus, when large AZFa and AZFb microdeletions are detected there is theoretically no chance to find testicular spermatozoa. If only AZFc microdeletions are present, testicular biopsy is possible with a good chance of mature spermatozoa retrieval before microinjection, and AZFc microdeletions are also often present (10%) in cases of severe oligospermia. Couples must be informed of genomic deletions and a genetic counseling is essential to explain the potential childhood risks after assisted reproductive techniques. This problem has been discussed by the French "High Authority of Health". It recommends determination of these Y microdeletions when oligozoospermia is severe (lower than one million spermatozoa per milliliter).

The utility of 1- and 3-month protocol biopsies on renal allograft function: a randomized controlled study.

Identification of pathological events in the renal allograft using protocol biopsies at predetermined time intervals may yield useful information and improve outcomes. We examined the influence of decisions taken on the basis of 1- and 3-month protocol biopsies findings on 1-year renal allograft function in a prospective randomized study. Out of 102 living-donor allograft recipients, 52 were randomized to undergo protocol biopsies and 50 controls had only indicated biopsies. All acute rejection (AR) episodes (clinical and subclinical) were treated. Calcineurin inhibitor (CNI) dose adjustments were made on clinical judgment. Baseline recipient and donor characteristics, immunosuppressive drug usage, HLA matches and 2-h cyclosporine levels were similar in both groups. At 1 and 3 months, protocol biopsies revealed borderline (BL) changes in 11.5% and 14% patients, AR in 17.3% and 12% and chronic allograft nephropathy (CAN) in 3.8% and 10%. The incidence of clinically evident AR episodes was similar in the two groups, but biopsy group had lower serum creatinine at 6 months (p = 0.0003) and 1 year (p < 0.0001). The renal functions were similar in those with normal histology and BL changes. Protocol biopsies are helpful in detecting subclinical histological changes in the graft and improving short-term renal allograft function.

Recurrent glomerulopathy in the renal allograft.

The renal allograft is prone to develop almost all forms of glomerular diseases either as recurrent or de novo disease, with the exception of Alport's syndrome. Identification of recurrent glomerulonephritis requires an accurate diagnosis of pretransplant disease, which may not always be possible as it presents as end-stage renal disease at the time of transplantation. Posttransplantation glomerular diseases such as chronic allograft nephropathy, malignant hypertension, and thrombotic microangiopathy due to various causes may be mistaken for primary glomerulonephritis. In this article, an attempt has been made to identify the glomerular diseases that were detected in renal allografts over a 9-year period, comprising 950 cases in a tertiary care center in north India.

Oxidative status in stable renal transplantation.

Increased oxidative stress and hyperhomocysteinemia are frequently observed in patients with end-stage renal disease. The effects of kidney transplantation on oxidative state are incompletely understood. With an aim to evaluate the prevalence and severity of oxidative stress in living donor renal transplant recipients, we conducted a cross-sectional study. Thirty-five renal transplant recipients (mean age 34 years; body mass index 21.93 +/- 1.92) with normal renal function (mean serum creatinine 1.41 +/- 0.33 mg%) were enrolled in the study. All patients were on cyclosporine-based immunosuppression. We assessed serum nitric oxide (NO) levels, plasma total homocysteine levels (tHCy), and malonaldehyde (MDA) levels. We evaluated the antioxidant power ferric reducing ability of plasma (FRAP) assay. The mean duration to the first sampling was 9.23 months after transplantation. Fourteen age- and sex-matched normotensive people were used as controls. The mean tHCy was significantly higher among patients (15.29 +/- 0.66 mmol/L compared with controls (9.58 +/- 2.90 mmol/L; P < .05). The MDA levels in patients (6.405 +/- 2.05 nmol/mL) were comparable to controls (6.093 +/- 1.93 nmol/mL; P = .099). The status of antioxidative power as measured by FRAP showed a trend to higher antioxidative status (697.57 +/- 103.07 mmol/L) in patients compared with controls (518 +/- 120.99 mmol/L; P = NS). The mean NO levels in patients (545.01 +/- 281.49 mmol/mL) were significantly higher than controls (183.49 +/- 64.53 nmol/mL; P < .05). Stable renal transplant recipients display a pattern of increased oxidant stress that may be counterbalanced by an enhanced antioxidant mechanisms.

Comparison of enteric-coated mycophenolate sodium with mycophenolate mofetil in living renal allograft transplantation.

OBJECTIVE: Enteric-coated mycophenolate sodium (MPS) has been developed to decrease the GI side effects of mycophenolate mofetil (MMF). We did a retrospective analysis of 112 patients to compare the safety and efficacy of enteric coated MPS vs MMF in living renal transplantation. METHODS: Patients were divided into two groups. Group A who received MPS [Novartis, Basel, Switzerland] [1.08-1.44 g/d] included 53 patients of mean age 33.5 +/- 11.9 yrs, and M:F gender ratio 37:15 with a mean donor age of 43.2 +/- 9.9 years. Group B who received MMF [1.5-2.0 g/d] included 59 subjects of mean age 33.2 +/- 9.9 yrs and M:F gender ratio 57:6, with a mean donor age of 41.4 +/- 10.9 years. All patients received cyclosporine and prednisolone in addition to mycophenolate. Mean follow-up in the two groups was 11.6 +/- 7.0 and 12.6 +/- 8.5 months, respectively. RESULTS: There were 11 (20.7%) rejection episodes in Group A and 12 (20.3%) rejection episodes in Group B (P = NS). Incidence of CMV disease was 9.61% and 10.1%, and of other infections, 88.7% and 74.7% in Groups A and Group B, respectively [P = NS]. The incidence of GI (18.9% & 20.3%) and hematologic toxicities (9.4% & 5.1%) were similar in the groups. Patient and graft survivals in Group A were 91.9% & 86.6%, and in Group B was 91.3% & 91.3%, respectively [P = NS]. CONCLUSION: Mycophenolate sodium is an alternative immunosuppressant to mycophenolate mofetil in kidney transplant recipients with a similar efficacy and safety profile.

Comparison of generic cyclosporine microemulsion versus neoral in de novo renal transplant recipients managed by 2-hour postdose monitoring.

INTRODUCTION: The bioequivalence of generic formulations is established by measuring pharmacokinetic parameters in healthy volunteers. Cyclosporine (CsA) absorption and exposure is known to differ between healthy volunteers and transplant recipients. Therefore bioequivalence testing may be inadequate to ensure therapeutic equivalence. We sought to compare the efficacy of generic cyclosporine (ArpimuneME, RPG Life Sciences) versus Sandimmune Neoral in de novo renal transplant recipients. METHODS: A prospective single-center, open-label study enrolled 20 de novo renal transplant patients (group 1: mean age 30.55 +/- 9.81 years, M:F 19:1, mean donor age 43.4 +/- 10.8). All patients received ArpimuneME along with azathioprine and prednisolone. The results were compared with 17 matched controls (group 2: mean age 28.1 +/- 9.5 years, M:F 13:4, mean donor age 47.8 +/- 6.8) who received Neoral and were transplanted during the same period. C(2) levels were monitored by the cloned enzyme donor immunoassay (CEDIA). RESULTS: Patient and graft survivals were 100% and 100% and 100% and 92.8% in groups 1 and 2, respectively (P = NS). Six patients (30%) experienced rejection in group 1 as compared eight patients (47.1%) in group 2. Mean CsA levels (ng/mL) during the first month were 1419.1 +/- 213.6 and 1460.5 +/- 290.7 and at 3 months, 1296.3 +/- 227.8 and 1342.4 +/- 303.4 in the two groups, respectively (P = NS). The mean serum creatinine levels (mg%) in group 1 and group 2 were 1.6 +/- 0.8 and 2.0 +/- 1.4 at discharge and 1.5 +/- 0.4 and 1.5 +/- 0.8 at 6 months, respectively (P = NS). CONCLUSION: Use of a generic microemulsion form of CsA provided safe and effective immunosuppression compared with Sandimmune Neoral when drug monitoring was performed by C(2) levels.

Treatment of oropharyngeal cancer in renal transplant recipients without cessation of immunosuppressive therapy.

INTRODUCTION: Renal transplantation and immunosuppression are associated with an increased incidence of malignancy. Reduction or cessation of immunosuppressive therapy has been advocated in these cases to prevent tumor progression and recurrence. We evaluated the outcome of treatment of oropharyngeal cancer (OC) after renal transplantation without cessation of immunosuppressive therapy. METHODS: The database of patients with OC after renal transplantation was analyzed with respect to age, sex, type of immunosuppression, interval between transplantation and diagnosis of cancer, as well as method of treatment and survival. RESULTS: Thirty one (2.06%) renal transplant recipients developed malignancy including 6 (20%) with OC. Lingual cancer was seen in three, and one each showed an isolated tonsillar lymphoma, a parotid carcinoma, or a carcinoma of the larynx with only the last having had two other malignancies in the past. Three subjects were on immunosuppression with azathioprine and prednisolone, and the others were prescribed cyclosporine and prednisolone. Average time from transplantation to diagnosis of OC was 106 months. The interval was the shortest (2 years) for tonsillar lymphoma in an 18-year-old patient who received cyclosporine and showed features of left follicular tonsillitis. The patient with advanced carcinoma of the larynx did not receive any treatment and succumbed within 3 months. The dose of cyclosporine was reduced in the lymphoma case but immunosuppression was not altered in the other patients. All subjects were treated with a standard protocol. During a mean follow-up of 33 months, one had local recurrence of parotid carcinoma and the others showed well functioning renal grafts. CONCLUSION: Comprehensive treatment of OC after renal transplantation without withdrawing the immunosuppression prolonged the life of these patients with functioning grafts.