Outcomes Following Surgical Interventions for Isolated Lunotriquetral Interosseous Ligament Injuries: A Systematic Review.

Ulnar-sided wrist pain can be attributed to various bony and ligamentous structures. The purpose of this review is to compare outcomes following surgical interventions for isolated lunotriquetral (LT) interosseous ligament injuries in adults. We assessed 202 procedures from 9 retrospective case series studies of low to moderate quality based on the Structured Effectiveness Quality Evaluation Scale. The comparative outcomes (ie, range of motion, pain, strength, quality of life, complications, return to work, and patient satisfaction) were aggregated and categorized under arthrodesis, capsulodesis, ligament repairs and reconstruction, and ulna shortening osteotomy procedures. Although the comparison of outcomes was largely inconclusive due to the heterogeneity and the omission of preoperative characteristic data, we did observe higher complications and reoperation rates post LT arthrodesis. It is recommended that all outcomes be standardized and presented uniformly with best practices developed to better characterize the injury's severity and integrity in future studies.

Relationship of Creatinine and Cystatin C-based Estimated Glomerular Filtration rates with Measured Glomerular Filtration Rate in Healthy Kidney Donors from South Asia.

Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation is currently recommended for the estimation of glomerular filtration rate (GFR). This retrospective study aimed to evaluate the correlation between creatinine and cysC-based estimated GFRs and measured GFR in healthy adults. Consecutive healthy adults who were accepted as voluntary kidney donors at our center between January 2008 and December 2012 were included in the study. The 336 individuals who comprised the study population had a mean age of 41.6 ± 11.8 years, male:female ratio 1:1.7, mean creatinine 0.9 ± 0.1 mg/dl, and mean cysC 0.8 ± 0.1 mg/dl. Mean measured GFR by Tc-99m diethylenetriaminepentaacetic acid using Gates method was 98.4 ± 21.2 ml/min/1.73 m2. The mean ± standard deviation of eGFRs by various formulae were as follows: Cockcroft-Gault (CG) = 88.1 ± 15.9 ml/min/1.73 m2, Modification of Diet in Renal Disease (MDRD) = 78 ± 14.7 ml/min/1.73 m2, CKD-EPI creatinine = 88.1 ± 15.5 ml/min/1.73 m2, CKD-EPI cysC = 97 ± 19.9 ml/min/1.73 m2, CKD-EPI creatinine-cysC (CKD-EPI cr-cysC) = 92.5 ± 14.1 ml/min/1.73 m2. The CKD-EPI cr-cysC equation had the highest accuracy, with 43% and 72% of values lying within ±10% and ±20% of the measured GFR, respectively. Bland-Altman analyses for levels of agreement showed least bias with CKD-EPI cysC overall and among females, while among males, CKD-EPI creatinine equation had the least bias. The CKD-EPI equation showed a higher performance than the MDRD and CG equation in GFR estimation of a healthy population. Among CKD-EPI equations, CKD-EPI cr-cysC had the highest accuracy and CKD-EPI cysC the least bias.

An integrated hybrid microfluidic device for oviposition-based chemical screening of adult Drosophila melanogaster.

Chemical screening using Drosophila melanogaster (the fruit fly) is vital in drug discovery, agricultural, and toxicological applications. Oviposition (egg laying) on chemically-doped agar plates is an important read-out metric used to quantitatively assess the biological fitness and behavioral responses of Drosophila. Current oviposition-based chemical screening studies are inaccurate, labor-intensive, time-consuming, and inflexible due to the manual chemical doping of agar. In this paper, we have developed a novel hybrid agar-polydimethylsiloxane (PDMS) microfluidic device for single- and multi-concentration chemical dosing and on-chip oviposition screening of free-flying adult stage Drosophila. To achieve this, we have devised a novel technique to integrate agar with PDMS channels using ice as a sacrificial layer. Subsequently, we have conducted single-chemical toxicity and multiple choice chemical preference assays on adult Drosophila melanogaster using zinc and acetic acid at various concentrations. Our device has enabled us to 1) demonstrate that Drosophila is capable of sensing the concentration of different chemicals on a PDMS-agar microfluidic device, which plays significant roles in determining oviposition site selection and 2) investigate whether oviposition preference differs between single- and multi-concentration chemical environments. This device may be used to study fundamental and applied biological questions in Drosophila and other egg laying insects. It can also be extended in design to develop sophisticated and dynamic chemical dosing and high-throughput screening platforms in the future that are not easily achievable with the existing oviposition screening techniques.

Agar-polydimethylsiloxane devices for quantitative investigation of oviposition behaviour of adult Drosophila melanogaster.

Drosophila melanogaster (fruit fly) is a model organism and its behaviours including oviposition (egg-laying) on agar substrates have been widely used for assessment of a variety of biological processes in flies. Physical and chemical properties of the substrate are the dominant factors affecting Drosophila's oviposition, but they have not been investigated precisely and parametrically with the existing manual approaches. As a result, many behavioral questions about Drosophila oviposition, such as the combined effects of the aforementioned substrate properties (e.g., exposure area, sugar content, and stiffness) on oviposition and viability, and their threshold values, are yet to be answered. In this paper, we have devised a simple, easily implementable, and novel methodology that allows for modification of physical and chemical composition of agar substrates in order to quantitatively study survival and oviposition of adult fruit flies in an accurate and repeatable manner. Agar substrates have been modified by surface patterning using single and hexagonally arrayed through-hole polydimethylsiloxane (PDMS) membranes with various diameters and interspacing, as well as by substrate stiffness and sugar content modification via alteration of chemical components. While pure PDMS substrates showed a significant lethal effect on flies, a 0.5 mm diameter through-hole access to agar was found to abruptly increase the survival of adult flies to more than 93%. Flies avoided ovipositing on pure PDMS and on top of substrates with 0.5 mm diameter agar exposure areas. At a hole diameter of 2 mm (i.e., 0.25% exposure area) or larger, eggs were observed to be laid predominately inside the through-holes and along the edges of the PDMS-agar interface, showing a trending increase in site selection with 4 mm (i.e., 1% exposure area threshold) demonstrating natural oviposition rates similar to pure agar. The surface-modified agar-PDMS hybrid devices and the threshold values reported for the substrate physical and chemical conditions affecting oviposition are novel; therefore, we advocate their use for future in-depth studies of oviposition behaviour in Drosophila melanogaster with accuracy and repeatability. The technique is also useful for development of novel assays for learning and decision-making studies as well as miniaturized devices for self-assembly of eggs and embryonic developmental investigations.

Adefovir nephrotoxicity in a renal allograft recipient.

Adefovir dipivoxil, an oral prodrug of adefovir, is used in the treatment of lamivudine-resistant hepatitis B virus (HBV) infection. Nephrotoxicity manifesting as proximal renal tubular dysfunction and acute tubular necrosis (ATN) were commonly reported in the past, when higher doses were used for the treatment of human immunodeficiency virus infection. However, nephrotoxicity is rare at lower doses that are currently recommended for the treatment of HBV infection. A 31-year-old female was detected to be hepatitis B surface antigen positive months after a kidney transplant. The patient was initiated on lamivudine, but developed resistance after 1 year of treatment, at which time low-dose adefovir was added. The patient developed renal allograft dysfunction after 10 months of starting adefovir. Serum creatinine increased from 1.1 mg/dl to 1.9 mg/dl, along with progressively increasing sub-nephrotic proteinuria. Renal allograft biopsy revealed features of ATN. After discontinuation of adefovir, proteinuria resolved and renal dysfunction improved slowly over the next 2 years. Adefovir-induced nephrotoxicity, although uncommon at lower doses, needs to be considered in the differential diagnosis of renal dysfunction and sub-nephrotic proteinuria occurring in patients receiving adefovir for prolonged periods.

Profile of incident chronic kidney disease related-mineral bone disorders in chronic kidney disease Stage 4 and 5: A hospital based cross-sectional survey.

Chronic kidney disease related-mineral bone disorder (CKD-MBD) has been poorly studied in pre-dialysis Indian CKD patients. We aimed to study the clinical, biochemical and extra skeletal manifestations of untreated CKD-MBD in pre-dialysis Stage 4 and 5 CKD patients attending nephrology out-patient clinic at a tertiary care hospital in South India. A hospital based cross-sectional survey including, demographic profile, history of CKD-MBD symptoms, measurement of serum calcium, phosphate, parathyroid hormone, 25 hydroxy vitamin D (25(OH) D) and alkaline phosphatase; lateral abdominal X-rays for abdominal aortic calcification (AAC) and echocardiography for valvular calcification (VC) was carried out. Of the 710 patients surveyed, 45% had no CKD-MBD related symptom. Prevalence of hypocalcemia, hyperphosphatemia, hyperparathyroidism (>150 pg/mL) and 25(OH) D levels <30 ng/mL was 66.3%, 59%, 89.3% and 74.7% respectively. Echocardiography was carried out in 471 patients; 96% of whom had VC (calcification score ≥1). Patients with VC were older and had lower 25(OH) D levels than those without. Lateral abdominal X-rays were obtained in 558 patients, 6.8% of whom were found to have AAC, which was associated with older age. Indian patients with incident CKD-MBD have a high prevalence of hypocalcemia, 25(OH) D deficiency and VC even prior to initiating dialysis while AAC does not appear to be common. The association between 25(OH) D deficiency and VC needs further exploration.

Posterior reversible encephalopathy syndrome in a renal allograft recipient: A complication of immunosuppression?

Posterior reversible encephalopathy syndrome (PRES) is an uncommon post-renal transplant complication. We report a 16-year-old boy who had an acute cellular rejection immediate post-transplant and was given intravenous methylprednisolone along with an increase in tacrolimus dose. He was diagnosed to have PRES based on clinical and radiological features within 6 h of intensified immunosuppression. This is an unusual case report of successfully managing PRES with continuation of the intensified immunosuppression as warranted by the clinical situation, along with aggressive blood pressure control. After 6 weeks, magnetic resonance imaging showed complete resolution of lesions. He has good graft function and no residual neurological deficits while on small doses of three antihypertensives, 12 months after transplantation.

Extensive emphysematous pyelonephritis in a renal allograft treated conservatively: case report and review of the literature.

Emphysematous pyelonephritis (EPN) is a rare occurrence in renal allografts. An aggressive approach resulting in transplant nephrectomy is viewed as the standard of care. Over the recent years, treatment with percutaneous drainage (PCD) of the renal and perinephric collections and appropriate antibiotics has been reported with good success in lesser grades of this infection. Only 4 cases of extensive EPN disease with Escherichia coli, treated with conservative management, are reported in the English-language literature. We present a case of severe EPN caused by Klebsiella pneumoniae, successfully managed with early PCD, and propose a step-up strategy aimed toward graft preservation.

Infections with atypical mycobacteria in renal transplant recipients.

Infections due to atypical mycobacteria are infrequent in renal transplant recipients but they cause serious morbidity. These pathogens are common in patients with acquired immune deficiency syndrome (AIDS). We report four proven cases of infections caused with atypical mycobacteriae from 1997 to 2003, by different organisms namely, M. chelonei, M.fortuitum, M. abcessus and M. terrae in renal transplant recipients. Infection with M. terrae documented here is the first occurrence in a renal transplant patient. Histopathological examination of aspirates or biopsy specimens from involved areas and staining and culture for mycobacteriae are essential for diagnosis. Treatment involves antimycobacterial therapy, reduction in immunosuppression and surgery, if indicated. Atypical mycobacterial infections, though currently uncommon, are significant and could prove to be an emerging pathogen in renal transplant recipients in the context of the AIDS epidemic in India.

Pre-tertiary hospital care of patients with chronic kidney disease in India.

BACKGROUND & OBJECTIVES: There is paucity of data available on how chronic kidney disease (CKD) is treated before referral to a tertiary hospital. This study was conducted to assess pre-tertiary hospital care of patients with CKD 5 at their presentation to nephrology services at a tertiary care hospital. METHODS: Over a period of 8 months, consecutive patients with CKD 5 presenting at the Nephrology services at Christian Medical College, Vellore, Tamil Nadu, and their relatives were interviewed to assess the pre-tertiary hospital care and knowledge about CKD 5 and its treatment. RESULTS: A total of 561 patients with CKD 5 were enrolled. The mean duration (months) of known CKD was 12.4 +/- 23.1 and known CKD 5 was 3.2 +/- 3.5. Of these, 369 patients (65.8%) had been under the care of a nephrologist; 305 patients had CKD 5 as the initial presentation of renal illness. Vaccination against hepatitis B had been initiated in only 133 patients (23.7%). Only 172 patients(38%) had an adequately controlled blood pressure. Care under a nephrologist was more likely to result in appropriate investigation, treatment and patient education though blood pressure control did not differ. INTERPRETATION & CONCLUSION: Paucity of symptoms in the initial stages of certain forms of CKD probably led to 50 per cent of patients presenting with CKD 5 as the initial presentation of renal disease. Inadequate vaccination against hepatitis B infection highlights the need for appropriate vaccination. Prevention of CKD and its progression are important targets which requires physician awareness at all levels. Early referral to a nephrologist's care is more likely to result in appropriate investigations and treatment.

Acute graft pyelonephritis following renal transplantation.

BACKGROUND: Urinary tract infection is the most common form of bacterial infection encountered in a renal transplant recipient. Studies explaining the long-term consequences of acute graft pyelonephritis (AGPN) are few. METHODS: A total of 1022 consecutive renal allograft recipients were studied retrospectively over a period of 10 years for evidence of AGPN. These patients were classified into two groups according to the presence or absence of at least one AGPN episode. Only culture-proven infections were included in the study. RESULT: Of the 1022 renal transplant recipients, 169 patients (16.5%) developed AGPN. In the multivariate analysis with stepwise logistic regression, significant associations were observed between AGPN and placement of ureteric stent (odds ratio [OR]=4.6), urological malformations of native kidney (OR=2.1), cytomegalovirus (CMV) disease (OR=2.0), mycophenolate mofetil (MMF)-based regimen (OR=1.9), and acute rejection episodes (OR=1.5). However, age>40 years, female gender, induction therapy, anti-CD3 treatment, and hyperglycemia did not show such an association. In comparison with the non-AGPN group, these patients had a lower graft and patient survival (though it did not attain statistical significance). In the multivariate analysis using the Cox model for the entire study population, AGPN did not independently contribute to poor graft or patient survival. CONCLUSION: AGPN in the renal transplant setting is an ominous event, as these patients are also more prone to develop bacteremia, acute rejection, and CMV disease, which could then lead to poor graft and patient survival. Its association with MMF needs further clarification.

Spectrum of severe chronic kidney disease in India: a clinicopathological study.

BACKGROUND: The healthcare burden due to chronic kidney disease has increased worldwide in the past decade. Elucidating the aetiology of chronic kidney disease may help in identifying strategies for prevention, both in the population and the Individual patient. Only a clinicopathological study can define the exact spectrum of chronic kidney disease since epidemiological studies have not shown a consistent aetiological profile. The histological evidence used to support the diagnosis varies with the degree to which renal biopsy is done. Renal biopsy is the gold standard in making an aetiological diagnosis in renal failure, but as a diagnostic tool in chronic kidney disease it is underutilized. METHODS: This prospective study done at Christian Medical College, Vellore in southern India from 1998 to 2003 aimed to determine the aetiological profile of severe chronic kidney disease by analysing renal biopsies. The value of pre-renal biopsy clinical Judgement in predicting the histological diagnosis was also assessed. Patients with diabetic nephropathy were excluded from the study. RESULTS: Four hundred and fifty-seven patients had evidence of chronic kidney disease as evidenced on biopsy as well as on clinical parameters. Three hundred and twenty-two of these patients (70.5%) had glomerulonephritis as the histological diagnosis. Fifty-five (12%) had Interstitial nephritis, 30 (6.6%) had hypertensive arteriosclerosis and 28 (6.1%) had metabolic nephropathies. The positive predictive value of a pre-biopsy clinical diagnosis in predicting interstitial nephritis was very low (33%). A large number of patients clinically diagnosed to have chronic interstitial nephritis had other aetiologies of chronic kidney disease. CONCLUSION: Glomerulonephritis was the most common cause of chronic kidney disease, not including diabetic nephropathy, followed by interstitial disease and benign arterionephrosclerosis. In patients with unidentified severe chronic kidney disease, renal biopsy provided an aetiological diagnosis.

A prospective evaluation of leflunomide therapy for cytomegalovirus disease in renal transplant recipients.

AIM: A preliminary observation suggests leflunomide is effective in the treatment of cytomegalovirus (CMV) disease in renal transplant recipients. A prospective evaluation was conducted in renal transplant recipients to study the efficacy of leflunomide in the treatment of CMV disease. PATIENTS AND METHODS: With prior approval and informed consent for therapy and follow-up, 17 consecutive consenting renal transplant recipients with proven CMV disease were treated with leflunomide. CMV disease was defined as a clinical syndrome of fever and/or symptoms of organ involvement, leukopenia, and a positive nested CMV quantitative PCR test at 0.001 microg/5 microL template input, with or without histologic evidence of tissue invasion. Leflunomide metabolite concentrations (A77 1726) were monitored. RESULTS: Of the 17 patients, 14 patients were treated for 6 months for CMV disease the first time; the remaining 3 received leflunomide treatment for relapse after ganciclovir treatment, for a year. Seven patients had fever with viremia and no organ involvement, nine had viremia with involvement of gastrointestinal tract, and one had fever with CMV inclusions in the allograft, with no demonstrable viremia. The three patients with relapse treated with leflunomide responded. Overall, 15 patients (88%) clinically responded to leflunomide therapy and with viral clearance from blood and healing of involved organs. The cost of therapy with intravenous ganciclovir (Cymevene, Roche) for 2 weeks was US 721 dollars while that of leflunomide (Cleft, Cipla Ltd) for 6 months was US 64 dollars. CONCLUSION: Leflunomide treatment for CMV disease in renal transplant recipients is effective, simple, and economical.

Pre- and postrenal transplantation pharmacokinetics of cyclosporine microemulsion.

UNLABELLED: The availability of a microemulsion formulation (ME) of cyclosporin (CyA) displays improved bioavailability and reduced inter and intra-patient variability, resulting in improved long-term outcomes. Recent developments in therapeutic drug monitoring stress the need to optimize peak drug levels during the early posttransplant period to obtain long-term benefit. METHODS: We studied early CyA-ME pharmacokinetics, comparing pre- versus immediate posttransplant values, to assess predictability of pre-transplant profiles in 22 patients including 3 diabetics. An 8 mg/kg per day amount in two divided doses was administered, for 5 days pretransplant and 10-14 days posttransplant before performing the pharmacokinetic studies. Drugs interacting with CyA metabolism/absorption were withdrawn and patients with liver disease were excluded the CyA level monitoring used a 5-point blood sampling (at 0 hours, 1 hours, 2 hours, 3 hours, and 4 hours post-dose). The study compared actual concentrations at each individual time and the limited 0-4 hour AUC. RESULTS: The paired values at each point pre- and posttransplant were: C0 = 171 +/- 63 and 215 +/- 112, C1 = 723.86 +/- 345 and 1239.95 +/- 415, C2 = 972 +/- 185 and 1249.95 +/- 336, C3 = 822 +/- 242 and 942.7 +/- 286, and C4 = 601.54 +/- 190 and 670.5 +/- 208 ng/mL respectively. The C1 and C2 values were significantly higher posttransplant (P =.008 and 0.0045 respectively), suggesting a steeper absorption phase, a conclusion consistent with the higher 0-4 hour AUC posttransplant (P =.0089). However, linear regression analysis of pre- versus posttransplant values showed poor correlations. CONCLUSIONS: CyA absorption is significantly lower among patients on maintenance hemodialysis and showed no predictive correlation with posttransplant levels. The possible role of uremia in retarding absorption which may have clinical significance for primary graft dysfunction, needs further evaluation.

Problems of classification of Henoch Schonlein purpura: an Indian perspective.

A 2-year prospective study was carried out in which 71 patients with primary cutaneous vasculitis were classified using the American College of Rheumatology (ACR) classification and the Chapel Hill Consensus Conference (CHCC) recommendations for Henoch Schonlein purpura (HSP). The sensitivity of the ACR criteria was 64.8% and that of the CHCC definition 31%. When the ACR criteria were combined with results of direct immunofluorescence (DIF) the sensitivity was 78.9%. The concordance between the two systems was low as only 12 patients fulfilled criteria for both classifications. Although the ACR criteria were found to be more useful in the classification of HSP our data suggest that they need to be modified to include adults with disease. The age at onset of disease was higher than that in the west. Seventy per cent of patients identified by either classification were > 20 years of age. The prevalence of gut involvement, microhaematuria and proteinuria was < 25% in both groups. The sensitivity of histopathology on the other hand was 80.4% and was not influenced by the duration of the lesion. The DIF test was a useful adjunct to histopathology if it was done within 48 h as the yield of a positive test was significantly higher in this group as compared to the patients who had the test done later.

Risk factors for post-transplant tuberculosis.

BACKGROUND: Post-transplant tuberculosis (post-TxTB) occurs in 12 to 20% of patients in India and results in the death of 20 to 25% of those patients. Prospective studies on post-TxTB are few. METHODS: Renal allograft recipients were studied prospectively for 3.1 (0 to 13.9) median (range) years for incidence, manifestations, risk factors, and prognosis for post-TxTB. Kaplan-Meier analysis was used to study the survival rates. The extended Cox proportional model for time-dependent covariates was used to measure the risk factors when the hazard was nonuniform. RESULTS: Of the 1414 patients considered for inclusion, multiple-transplant subjects (N = 37) and patients who developed pre-transplant TB (pre-TxTB; N = 126) were excluded from the study. The prevalence of post-TxTB was 13.3% (N = 166). The risk of post-TxTB when on cyclosporine (CsA) therapy was 2.5 (P = 0.0311) and 1.9 (P = 0.0430) times at < or =6 and < or =12 months, respectively, compared with patients on prednisolone plus azathioprine (PRED + AZA). The risk of post-TxTB in the presence of diabetes mellitus, chronic liver disease, and other co-existing infections [including deep mycoses, cytomegalovirus (CMV), Pneumocystis carinii pneumonia (PCP), nocardia] was 2.2 (P = 0.0011), 1.7 (P = 0.0010) and 2.4 (P < 0.0001) times, respectively. Of the 166 patients with post-TxTB, 53 patients died, and of those deaths, 17 (32%) were due to post-TxTB; 11 (65%) of the 17 had co-existing infections. The factors associated with death were HLA mismatches, PRED + AZA immunosuppression, pre- and post-TxTB, diabetes mellitus, post-transplant diabetes (PTDM), and other co-existing infections. The extended Cox model for death as the outcome variable showed the following to be significant risk factors: post-TxTB> 2 years (P = 0.0036), chronic liver disease> 6 years (P = 0.0457), PTDM> 5 years (P = 0.0729), diabetes mellitus (P = 0.0091), human lymphocyte antigen match < or =1 antigen (P = 0.0134), two to three antigens (P = 0.0448), and the presence of other co-existing infections (P < 0.0001). CONCLUSIONS: Cyclosporine therapy is associated with early post-TxTB. Diabetes mellitus and chronic liver disease are risk factors for post-TxTB. The occurrence of both pre-TxTB and post-TxTB (>2 years) along with hyperglycemia, liver disease, and other co-existing infections are important risk factors for death.

Immunosuppression in live-related donor renal transplantation.

BACKGROUND: Triple immunosuppression with cyclosporine, azathioprine and prednisolone is the most common regimen employed following renal transplantation. No information is available regarding its impact on the results of renal transplantation in India. The present study is an audit of a fixed-dose cyclosporine-based immunosuppressive regimen in an exclusively live-related donor transplant programme, with specific regard to graft and patient outcomes. METHODS: Patients transplanted over a 3-year period and receiving cyclosporine-based immunosuppression were studied. The relationship between immunosuppression and graft outcomes [rejection episodes (RE), graft function, graft survival], and patient outcomes (patient survival) was analysed in those receiving triple immunosuppression. Dosage schedules were audited. Cyclosporine trough level monitoring was employed at graft dysfunction episodes, or at dose reduction points. RESULTS: The median follow up was 14 months. Triple drug immunosuppression was used in 191 patients and double drug therapy in 26. The overall one-year patient survival rate was 91% and the corresponding graft survival rate was 90%. An audit of dosing schedules showed that over the first 6 months post-transplant, cumulatively, 20%-50% of patients received azathioprine, and 55%-60% received cyclosporine in doses below the protocol. The immunosuppressive doses (both of cyclosporine and azathioprine) in the first month were significantly related to the RE (p < 0.01) in the first month and the total number of RE in the first 6 months (p < 0.01). The other predictors were younger recipient age and older donor age. The sixth-month serum creatinine level was predicted by the donor age, the level of serum creatinine in the first month and the total number of RE in the first 6 months post-transplant. While no specific predictors of graft loss were identified in this cohort, diabetic nephropathy (p = 0.000) as the native renal disease, and the total number of RE were strongly related to patient mortality. The occurrence of > or = 2 RE in the first 6 months was an independent predictor, increasing the risk of death in the first 2 years post-transplant by 2.3 (p = 0.0001, 95% CI: 1.5-3.4). CONCLUSIONS: Sub-therapeutic baseline immunosuppression in the early post-transplant period predisposes to acute RE. This has an impact not only on graft function but also forms an important proximate marker of mortality, as seen in this cohort. Thus, immunosuppressive drug dosage should be optimized and therapeutic drug level monitoring strategies should be preemptive rather than event related, especially in the early post-transplant period. While fixed-dose immunosuppressive drug schedules are widely followed, it is possible to fall short of the target unless a specific effort is made to meet and sustain schedules.