Longitudinal Lower Airway Microbial Signatures of Acute Cellular Rejection in Lung Transplantation.

Rationale: Acute cellular rejection (ACR) after lung transplant is a leading risk factor for chronic lung allograft dysfunction. Prior studies have demonstrated dynamic microbial changes occurring within the allograft and gut that influence local adaptive and innate immune responses. However, the lung microbiome's overall impact on ACR risk remains poorly understood. Objectives: To evaluate whether temporal changes in microbial signatures were associated with the development of ACR. Methods: We performed cross-sectional and longitudinal analyses (joint modeling of longitudinal and time-to-event data and trajectory comparisons) of 16S rRNA gene sequencing results derived from lung transplant recipient lower airway samples collected at multiple time points. Measurements and Main Results: Among 103 lung transplant recipients, 25 (24.3%) developed ACR. In comparing samples acquired 1 month after transplant, subjects who never developed ACR demonstrated lower airway enrichment with several oral commensals (e.g., Prevotella and Veillonella spp.) than those with current or future (beyond 1 mo) ACR. However, a subgroup analysis of those who developed ACR beyond 1 month revealed delayed enrichment with oral commensals occurring at the time of ACR diagnosis compared with baseline, when enrichment with more traditionally pathogenic taxa was present. In longitudinal models, dynamic changes in α-diversity (characterized by an initial decrease and a subsequent increase) and in the taxonomic trajectories of numerous oral commensals were more commonly observed in subjects with ACR. Conclusions: Dynamic changes in the lower airway microbiota are associated with the development of ACR, supporting its potential role as a useful biomarker or in ACR pathogenesis.

Risk Index Predicts Pediatric Heart Allograft Non-Utilization.

BACKGROUND: Children listed for heart transplantation face the highest waitlist mortality among all solid organ transplant patients (14%). Attempts at decreasing donor allograft non-utilization (41.5%) could potentially decrease waitlist mortality for pediatric heart transplant patients. Our aim was to quantify the non-utilization risk of pediatric donor heart allografts at the time of initial offering. METHODS: Using the United Network of Organ Sharing (UNOS) database, we retrospectively analyzed 8823 deceased donors (≤18 years old) data through univariable and multivariable analysis and logistic regression models. These factors were divided into a training (n = 5882) and validation set (n = 2941). Donor clinical characteristics and laboratory values were used to predict non-utilization of donor hearts. The multivariable analysis used factors that were significant from the univariable analysis (p-value < .05), and the pediatric non-utilization risk index (pDRSI) included significant factors from the multivariable analysis, producing an overall risk score for non-utilization. With these data, we created a non-utilization risk index to predict likelihood of donor allograft non-utilization. RESULTS: From the 24 potential factors that were identified from univariable analysis, 17 were significant predictors (p < .05) of pediatric heart non-utilization in the multivariable analysis. Low left ventricular ejection fraction (odds ratio (OR)-35.3), hepatitis C positive donor (OR-23.3), high left ventricular ejection fraction (OR-3.29), and hepatitis B positive donor (OR-3.27) were the most significant risk factors. The phDSRI has a C-statistic of 0.80 for the training set and 0.80 for the validation set. CONCLUSION: Using over 8000 donors, the phDSRI uses 17 significant risk factors to predict risk of pediatric heart donor allograft non-utilization.

Role of doppler ultrasound in detecting vascular complications in recipients of living donor liver transplant (LDLT).

OBJECTIVE: To determine the role of Doppler ultrasound in the detection of vascular complications in recipients of living donor liver transplant, keeping contrast-enhanced computerised tomography of abdomen as the gold standard. METHODS: The retrospective study was conducted from February 16 to April 1, 2022, at the Pakistan Kidney and Liver Institute and Research Centre, Lahore, Pakistan, and comprised data of living donor liver transplant recipients who had undergone contrast-enhanced computerised tomography of abdomen within 24 hours of Doppler ultrasound between January 2021 and January 2022. For the diagnosis of hepatic vascular complications, the diagnostic values of Doppler ultrasound parameters were derived by correlating Doppler ultrasound findings with contrast-enhanced computerised tomography results. Data was analysed using SPSS 20. RESULTS: Of the 35 patients, 24(68.6%) were men and 11(31.4%) were women. The overall mean age was 45.86±13.8 years. For hepatic artery thrombosis, the use of Doppler ultrasound criteria yielded a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%, 96.6%, 83.3%, 100%, and 97.1% respectively. For hepatic artery stenosis, overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy of Doppler ultrasound was 100%, 96.8%, 75%, 100% and 97.1% respectively. Doppler ultrasound parameters resulted in a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 100% each in detecting portal vein and hepatic venous outflow tract thrombosis. Overall, Doppler ultrasound sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy was found to be 100%, 88.8%, 89.4%, 100% and 94.2% respectively. CONCLUSIONS: Doppler ultrasound was adequate to document vascular complications after living donor liver transplant in majority of the cases with high accuracy and sensitivity.

Design of the Recombinant Influenza Neuraminidase Antigen Is Crucial for Its Biochemical Properties and Protective Efficacy.

Supplementing influenza vaccines with recombinant neuraminidase (rNA) antigens remains a promising approach for improving suboptimal vaccine efficacy. However, correlations among rNA designs, properties, and protection have not been systematically investigated. Here, we performed a comparative analysis of several rNAs produced by the baculovirus/insect cell system. The rNAs were designed with different tetramerization motifs and NA domains from a recent H1N1 vaccine strain (A/Brisbane/02/2018) and compared for enzymatic properties, antigenicity, stability, and protection in mice. We found that the enzymatic properties differ between rNAs containing the NA head domain versus the full ectodomain, the formation of higher-order rNA oligomers is tetramerization domain dependent, whereas the protective efficacy is more contingent on the combination of the tetramerization and NA domains. Following single-dose immunizations, an rNA possessing the full ectodomain and the tetramerization motif from the human vasodilator-stimulated phosphoprotein provided much better protection than an rNA with ∼10-fold more enzymatically active molecules that is comprised of the head domain and the same tetramerization motif. In contrast, these two rNA designs provided comparable protection when the tetramerization motif from the tetrabrachion protein was used instead. These findings demonstrate that individual rNAs should be thoroughly evaluated for vaccine development, as the heterologous domain combination can result in rNAs with similar key attributes that vastly differ in protection. IMPORTANCE For several decades, it has been proposed that influenza vaccines could be supplemented with recombinant neuraminidase (rNA) to improve efficacy. However, some key questions for manufacturing stable and immunogenic rNAs remain to be answered. We show here that the tetramerization motifs and NA domains included in the rNA construct design can have a profound impact on the biochemical, immunogenic, and protective properties. We also show that the single-dose immunization regimen is more informative for assessing the rNA immune response and protective efficacy, which is surprisingly more dependent on the specific combination of NA and tetramerization domains than common attributes for evaluating NA. Our findings may help to optimize the design of rNAs that can be used to improve or develop influenza vaccines.

Three decades' analysis of pediatric liver transplantation outcomes reveals limited long-term improvements.

BACKGROUND: The aim of this study was to assess improvements in long-term survival of pediatric patients after liver transplantation by analyzing outcomes in transplant recipients who survived beyond 1 year after transplantation. There has been a marked increase in the 1-year survival of pediatric patients, from 78% in transplant recipients between 1987 and 1990 to 95% in transplant recipients between 2011 and 2017. The long-term outcomes have not seen a similar trend, creating a disparity that warrants analysis. METHODS: We analyzed 13 753 pediatric patients who survived for 1 year after receiving orthotopic liver transplantation between 1987 and 2017. The study period was divided into six eras. Outcomes were analyzed using the Kaplan-Meier method for time-to-event analysis, and multivariable Cox regression. RESULTS: There were no significant gains in long-term outcomes among 1-year survivors over the past three decades. Log-rank tests for equality of survivor functions between each era and 1987-1990 were not statistically significant. Cause of death analysis revealed that although infections caused 20.6% of deaths in patients transplanted between 1987 and 1990, this number dropped to 5.6% in those transplanted between 2011 and 2017 (p = .01). Malignancy caused 10.6% of deaths in 1987-1990 but caused 22.2% of the deaths in 2011-2017 (p = .04). CONCLUSION: Despite the gratifying gains in short-term survival of pediatric patients, 1-year survivors have no significant improvements in long-term survival after undergoing a liver transplantation. Long-term sequelae of immunosuppression, such as malignancy and infection, continue to be the most common causes of death. This study highlights the necessity for better long-term management of immunosuppression.

Good outcomes after pediatric intraperitoneal kidney transplant.

BACKGROUND: Kidney transplantation in small children is technically challenging. Consideration of whether to use intraperitoneal versus extraperitoneal placement of the graft depends on patient size, clinical history, anatomy, and surgical preference. We report a large single-center experience of intraperitoneal kidney transplantation and their outcomes. METHODS: We conducted a retrospective review of pediatric patients who underwent kidney transplantation from April 2011 to March 2018 at a single large volume center. We identified those with intraperitoneal placement and assessed their outcomes, including graft and patient survival, rejection episodes, and surgical or non-surgical complications. RESULTS: Forty-six of 168 pediatric kidney transplants (27%) were placed intraperitoneally in children mean age 5.5 ± 2.3 years (range 1.6-10 years) with median body weight 18.2 ± 5 kg (range 11.4-28.6 kg) during the study period. Two patients (4%) had vascular complications; 10 (22%) had urologic complications requiring intervention; all retained graft function. Thirteen patients (28%) had prolonged post-operative ileus. Eight (17%) patients had rejection episodes ≤6 months post-transplant. Only one case resulted in graft loss and was associated with recurrent focal segmental glomerular sclerosis (FSGS). Two patients (4%) had chronic rejection and subsequent graft loss by 5-year follow-up. At 7-year follow-up, graft survival was 93% and patient survival was 98%. CONCLUSIONS: The intraperitoneal approach offers access to the great vessels, which allows greater inflow and outflow and more abdominal capacity for an adult donor kidney, which is beneficial in very small patients. Risk of graft failure and surgical complications were not increased when compared to other published data on pediatric kidney transplants.

Exogenous melatonin mitigates chromium toxicity in maize seedlings by modulating antioxidant system and suppresses chromium uptake and oxidative stress.

Melatonin, being an endogenous signaling molecule plays important role in plant growth and stress alleviation. The present study was conducted to evaluate the ameliorative role of melatonin against Cr toxicity in maize seedlings. The Cr toxicity (50, 100 and 200 µM) severely affected hydroponically grown seedlings growth in a dose-dependent manner; however, the melatonin (0.5 and 1.0 µM) application markedly restored toxicity-induced growth retardation. Higher dose of melatonin (1.0 µM) was more effective in case of lower Cr toxicity (50 and 100 µM). Exposure of 200 µM Cr caused 45% and 43% reduction in shoot and root lengths and more than 80% reduction in biomass. In case of 200 µM Cr toxicity, application of 1.0 µM MT effectively restored shoot and root lengths reduction (from 45 to 30%) and biomass decline (from 80 to around 60%). Biomass restoration by 1.0 µM melatonin under 50 and 100 µM Cr was even more pronounced bringing it near to control plants having no Cr exposure. Further, both melatonin levels also improved root tips, root diameter, root volume and root surface area that had been damaged by Cr exposure. The melatonin also alleviated Cr-induced chlorophyll and carotenoids inhibition, improved relative water content, and markedly lowered proline and MDA content in shoots. Lower accumulation of MDA and proline, and greater membrane stability indices indicate that the melatonin conferred better plant growth by playing the role of antioxidant and detoxifying oxidative stress creating substances. Although antioxidant enzymes viz. SOD, POD, CAT and APX activities were also elevated by MT, this increase was not significantly different in the most of cases. No significant difference in NPK contents of shoot was observed by Cr and melatonin application indicating the growth retardation being caused directly by Cr intrinsic toxicity and not by nutrients deficiency. The melatonin-based amelioration of Cr toxicity in maize seedlings seems as the result of its nature as antioxidant, and not by activation/elevation of antioxidative enzymatic system.

Allograft discard risk index for heart transplantation.

BACKGROUND: The numberof patients awaiting heart transplantation (HTx) substantially exceeds the number of donor hearts transplanted each year, yet nearly 65% of eligible donor hearts are discarded rather than transplanted. METHODS: Deceased organ donors listed within the UNOS Deceased Donor Database between 2010 and 2020 were reviewed. Those greater than 10 years old and consented for heart donation were included and randomly separated into training (n = 48 435) and validation (n = 24 217) cohorts. A discard risk index (DSRI) was created using the results of univariable and multivariable analyses. Discard data were assessed at DSRI value deciles, and stratum-specific likelihood ratio (SSLR) analysis and Kaplan-Meier survival function were used for mortality data. RESULTS: Factors associated with higher DSRI values included donor age > 45, LVEF, HBV-core antibodies, hypertension, and diabetes. The DSRI C-statistic was .906 in the training cohort and .904 in the validation cohort. The DSRI did not reliably predict 30-day or 1-year mortality after transplantation (C-statistic .539 and .532, respectively). CONCLUSIONS: The factors leading to heart allograft discard are not correlated to the same degree with post-transplant outcomes. This suggests that optimizing utilization of certain allografts with slightly higher risk of discard could increase the heart donor pool with limited impact on posttransplant mortality.

Elevated serum sodium in recipients of liver transplantation has a substantial impact on outcomes.

Dysnatremias are a rare but significant event in liver transplantation. While recipient pre-transplant hypernatremia has been demonstrated to increase post-transplant mortality, the degree of hypernatremia and the impact of its resolution have been less well characterized. Here, we used multivariate Cox regression with a comprehensive list of donor and recipient factors in order to conduct a robust multivariate retrospective database study of 54,311 United Network for Organ Sharing (UNOS) liver transplant patients to analyze the effect of pre-transplant serum sodium on post-transplant mortality, post-transplant length of hospitalization, and post-transplant graft survival. Mortality and graft failure increased in a stepwise fashion with increasing pre-transplant hypernatremia: 145 -150 mEq/L (HR = 1.118 and HR = 1.113), 150-155 mEq/L (HR = 1.324 and HR = 1.306), and > 155 mEq/L (HR = 1.623 and HR = 1.661). Pre-transplant hypo- and hypernatremia also increased length of post-transplant hospitalization: < 125 mEq/L (HR = 1.098), 125-130 mEq/L (HR = 1.060), 145 -150 mEq/L (HR = 1.140), and 150-155 mEq/L (HR = 1.358). Resolution of hypernatremia showed no significant difference in mortality compared with normonatremia, while unresolved hypernatremia significantly increased mortality (HR = 1.254), including a durable long-term increased mortality risk for patients with creatinine < 2 mg/dL and MELD < 25. Pre-transplant hypernatremia serves as a morbid prognostic indicator for post-transplant morbidity and mortality.

Pediatric discard risk index for predicting pediatric liver allograft discard.

BACKGROUND: Of the 600 pediatric candidates added to the liver waiting list annually, 100 will remain waiting while over 100 liver allografts are discarded, often for subjective reasons. METHODS: We created a risk index to predict discard to better optimize donor supply. We used the UNOS database to retrospectively analyze 17 367 deceased donors (≤18 years old) through univariate and multivariate logistic regression models. Deceased donor clinical characteristics and laboratory values were independent variables with discard being the dependent variable in the analysis. Significant univariate factors (P-value < .05) comprised the multivariate analysis. Significant variables from the multivariate analysis were incorporated into the pDSRI, producing a risk score for discard. RESULTS: From 17 potential factors, 11 were identified as significant predictors (P < .05) of pediatric liver allograft discard. The most significant risk factors were as follows: DCD; total bilirubin >10 mg/dL, and alanine transaminase (ALT) ≥500 IU/L. The pDSRI has a C-statistic of 0.846 for the training set and 0.840 for the validation set. CONCLUSION: The pDSRI uses 11 significant risk factors, including elevated liver function tests, donor demographics, and donor risk/type to accurately predict risk of pediatric liver allograft discard and serve as a tool that may maximize donor yield.

Factors associated with long-term graft survival in pediatric kidney transplant recipients.

Pediatric kidney transplant recipients generally have good outcomes post-transplantation. However, the younger age and longer life span after transplantation in the pediatric population make understanding the multifactorial nature of long-term graft survival critical. This investigation analyzes factors associated with 10-year survival to identify areas for improvement in patient care. Kaplan-Meier with log-rank test and univariable and multivariable logistic regression methods were used to retrospectively analyze 7785 kidney transplant recipients under the age of 18 years from January 1, 1998, until March 9, 2008, using United Network for Organ Sharing (UNOS) data. Our end-point was death-censored 10-year graft survival after excluding recipients whose grafts failed within one year of transplant. Recipients aged 5-18 years had lower 10-year graft survival, which worsened as age increased: 5-9 years (OR: 0.66; CI: 0.52-0.83), 10-14 years (OR: 0.43; CI: 0.33-0.55), and 15-18 years (OR: 0.34; CI: 0.26-0.44). Recipient African American ethnicity (OR: 0.67; CI: 0.58-0.78) and Hispanic donor ethnicity (OR: 0.82; CI: 0.72-0.94) had worse outcomes than other donor and recipient ethnicities, as did patients on dialysis at the time of transplant (OR: 0.82; CI: 0.73-0.91). Recipient private insurance status (OR: 1.35; CI: 1.22-1.50) was protective for 10-year graft survival. By establishing the role of age, race, and insurance status on long-term graft survival, we hope to guide clinicians in identifying patients at high risk for graft failure. This study highlights the need for increased allocation of resources and medical care to reduce the disparity in outcomes for certain patient populations.

Sclerosing Encapsulating Peritonitis in a Pediatric Patient Treated With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Sclerosing encapsulating peritonitis (SEP) is a rare chronic inflammatory condition characterized by small bowel encapsulation by a thick fibrocollagenous membrane. Patients with SEP often present with nonspecific symptoms, such as abdominal pain and distension, however some patients may present with symptoms suggestive of intestinal obstruction. Secondary SEP has been reported in patients undergoing peritoneal dialysis and has been recently described in adults following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). OBSERVATIONS: We report a clinical case of a 13-year-old female who presented with worsening abdominal pain and distension and persistent emesis who was found to have SEP 13 months following CRS and HIPEC for management of desmoplastic small round cell tumor and subsequently required operative intervention. CONCLUSION: Although there have been published reports of adult patients experiencing cases of SEP following CRS/HIPEC, this is the first published case of secondary SEP occurring in a pediatric oncology patient.

Hexachlorocyclohexane toxicity in water bodies of Pakistan: challenges and possible reclamation technologies.

Pakistan is an agro-economy country where hexachlorocyclohexane (HCH) pesticides are being used to improve crop productivity, as a result the risk of contamination of soil and sediment has been increased. HCH exhibits all the characteristics of persistent organic pollutants (POP), and was therefore added to the list of 'new POPs' in 2009. This review report revealed that the major rivers of Pakistan such as the Indus Basin, River Ravi, River Chenab and their tributaries all are contaminated with HCH and the highest residual concentration (4,090 ng/g) was detected in a pesticide burial ground in Hyderabad city. Major sources of HCH contamination were identified as agricultural runoff, discharge of untreated industrial effluents and surface runoff. In order to manage HCH pollution, various ex-situ and in-situ remediation techniques along with their merits and demerits are thoroughly reviewed. Among these, microbial bioremediation is a low cost, environment friendly, effective in-situ remediation technique for remediation of HCH. Overall, the information provided in this manuscript will provide a future reference to the scientific community and bridge the knowledge gap between HCH release in the environment and their mitigation through proper treatment methods.

Health risk assessment of hexachlorocyclohexane in soil, water and plants in the agricultural area of Potohar region, Punjab, Pakistan.

In this study analysis of soil, water and plant residue samples is presented to evaluate the contamination levels and possible health risks. Hexachlorocyclohexane (HCH) is a persistent organic pollutant used as a pesticide in agricultural sector for pest control in order to obtain higher productivity. For analysis soil, water and crop residue samples were collected from different agricultural areas of the northern Punjab region of Pakistan. The investigation of the samples shows significant levels of HCH residues in all types of samples. Gas chromatography-mass spectrometry analysis was used to assess the higher residue levels of HCH in the samples. The concentration of HCH residues detected in samples ranged from 2.43 to 8.88 µg/g in soil, nd -5.87 µg/l in water and nd - 4.87 µg/g in plants. The presence of HCH residues in soil, water and plant samples was beyond the recommended quality guidelines. Human health risk was evaluated for cancer and non-cancer risks through dietary and non-dietary exposure routes. The hazard index was HI > 1 in children and HI < 1 in adults, while the non-dietary incremental lifetime cancer risks (ILCR) were beyond the internationally acceptable limit of 1 × 10-5. Hence, results of the present investigation concluded the presence of high levels of HCH residues in samples and pose high health risk to the inhabitants. These findings are alarming and apprise the concerned departments for the remediation of contamination and proper implementation of environmental laws in the area.

The decreasing predictive power of MELD in an era of changing etiology of liver disease.

The field of liver transplantation has shifted considerably in the MELD era, including changing allocation, immunosuppression, and liver failure etiologies, as well as better supportive therapies. Our aim was to evaluate the predictive accuracy of the MELD score over time. The United Network for Organ Sharing provided de-identified data on 120 156 patients listed for liver transplant from 2002-2016. The ability of the MELD score to predict 90-day mortality was evaluated by a concordance (C-) statistic and corroborated with competing risk analysis. The MELD score's concordance with 90-day mortality has downtrended from 0.80 in 2003 to 0.70 in 2015. While lab MELD scores at listing and transplant climbed in that interval, score at waitlist death remained steady near 35. Listing age increased from 50 to 54 years. HCV-positive status at listing dropped from 33 to 17%. The concordance of MELD and mortality does not differ with age (>60 = 0.73, <60 = 0.74), but is lower in diseases that are increasing most rapidly-alcoholic liver disease and non-alcoholic fatty liver disease-and higher in those that are declining, particularly in HCV-positive patients (HCV positive = 0.77; negative = 0.73). While MELD still predicts mortality, its accuracy has decreased; changing etiology of disease may contribute.

Physiology and selected genes expression under cadmium stress in Arundo donax L.

The effects of cadmium stress (0, 25, 50, 75, and 100 mg/L) on morpho-physiological features and selected genes (carotenoid hydroxilase, amidase, GR, bHLH, NRAMP and YSL) expression were demonstrated in Arundo donax L. The plants were assessed for Cd uptake and its effects on chlorophyll and antioxidants after 30 days of exposure. The expression of genes conferring metal tolerance was evaluated after 10 days of Cd exposure. The results showed a maximum Cd uptake in roots (872 mg/kg) followed by stem (734 mg/kg) and leaves (298 mg/kg) at highest supplied Cd concentration. The Cd uptake reduced dry weight, Chla, Chlb, and total Chl contents of giant reed. The SOD, CAT, POD activities and MDA content increased at the maximum Cd concentration over control. The highest genes expression for carotenoid hydroxylase, glutathione reductase and amidase was observed in plants exposed to 100 mg/L. However, differential bHLH gene expression and slightly increased gene expression of NRAMP was noted for different Cd treatments. Amidase expressed under Cd stress which is pioneer report in A. donax. These results provided insights into the mechanisms of A. donax tolerance and survival under Cd Stress.

Using Temporal Covariance of Motion and Geometric Features via Boosting for Human Fall Detection.

Fall induced damages are serious incidences for aged as well as young persons. A real-time automatic and accurate fall detection system can play a vital role in timely medication care which will ultimately help to decrease the damages and complications. In this paper, we propose a fast and more accurate real-time system which can detect people falling in videos captured by surveillance cameras. Novel temporal and spatial variance-based features are proposed which comprise the discriminatory motion, geometric orientation and location of the person. These features are used along with ensemble learning strategy of boosting with J48 and Adaboost classifiers. Experiments have been conducted on publicly available standard datasets including Multiple Cameras Fall (with 2 classes and 3 classes) and UR Fall Detection achieving percentage accuracies of 99.2, 99.25 and 99.0, respectively. Comparisons with nine state-of-the-art methods demonstrate the effectiveness of the proposed approach on both datasets.

Therapeutic effect of atorvastatin on kidney functions and urinary excretion of Glimepiride in healthy adult human male subjects.

Glimepiride and atorvastatin in combination are commonly employed for treating the hyperglycemia and dyslipidemia, respectively, in patients of type 2 diabetes. The present study was designed to find out the influence of atorvastatin on urinary excretion and renal clearance of Glimepiride in healthy adult male volunteers. In each experimental subject, Glimepiride 2mg was given orally after an overnight fasting. Samples of blood and urine were taken at different specific time intervals. After a washout period of ten days, Glimepiride 2mg was co-administered with atorvastatin 20mg orally. Post-medication, blood and urine samples were collected following the same sampling schedule as for Glimepiride alone. The samples were analyzed for Glimepiride and creatinine concentration by HPLC-UV and Spectrophotometer, respectively. Mean (±SE) values for blood pH 7.445±0.05 and 7.382±0.05, urine pH 4.972±0.08 and 5.08±0.10, diuresis 0.0207±0.00 and 0.0237±0.00ml/min/kg, endogenous creatinine in plasma 9.048±0.33 and 8.613±0.024µg/ml, endogenous creatinine in urine 512.34±18.20 and 556.72±4.60µg/ml, Glimepiride plasma concentration 0.16069±0.00 and 0.3227±0.01µg/ml, Glimepiride urine concentration 1.5994±0.03 and 0.8665±0.04µg/ml, renal clearance of creatinine 1.224±0.09 and 1.550±0.09ml/min/kg, renal clearance of Glimepiride 0.2064±0.01 and 0.0641±0.00ml/min/kg and clearance ratio 0.1791±0.01 and 0.0414±0.00 were observed for Glimepiride alone and its concurrent administration with atorvastatin, respectively. Atorvastatin decreased the urinary excretion and renal clearance of Glimepiride due to which chances of hypoglycemia provokes and renal handling of Glimepiride involves back diffusion besides glomerular filtration and no influence of atorvastatin was seen on these mechanisms.