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Article ; Online: Impacts of High Intra- and Inter-Individual Variability in Tacrolimus Pharmacokinetics and Fast Tacrolimus Metabolism on Outcomes of Solid Organ Transplant Recipients

Charat Thongprayoon / Panupong Hansrivijit / Karthik Kovvuru / Swetha R. Kanduri / Tarun Bathini / Aleksandra Pivovarova / Justin R. Smith / Wisit Cheungpasitporn

Journal of Clinical Medicine, Vol 9, Iss 2193, p

2020 Volume 2193

Abstract: Tacrolimus is a first-line calcineurin inhibitor (CNI) and an integral part of the immunosuppressive strategy in solid organ transplantation. Being a dose-critical drug, tacrolimus has a narrow therapeutic index that necessitates periodic monitoring to ... ...

Abstract	Tacrolimus is a first-line calcineurin inhibitor (CNI) and an integral part of the immunosuppressive strategy in solid organ transplantation. Being a dose-critical drug, tacrolimus has a narrow therapeutic index that necessitates periodic monitoring to maintain the drug’s efficacy and reduce the consequences of overexposure. Tacrolimus is characterized by substantial intra- and inter-individual pharmacokinetic variability. At steady state, the tacrolimus blood concentration to daily dose ratio (C/D ratio) has been described as a surrogate for the estimation of the individual metabolism rate, where a low C/D ratio reflects a higher rate of metabolism. Fast tacrolimus metabolism (low C/D ratio) is associated with the risk of poor outcomes after transplantation, including reduced allograft function and survival, higher allograft rejection, CNI nephrotoxicity, a faster decline in kidney function, reduced death-censored graft survival (DCGS), post-transplant lymphoproliferative disorders, dyslipidemia, hypertension, and cardiovascular events. In this article, we discuss the potential role of the C/D ratio in a noninvasive monitoring strategy for identifying patients at risk for potential adverse events post-transplant.
Keywords	tacrolimus ; calcineurin inhibitors ; FK506 ; transplantation ; kidney transplantation ; immunosuppression ; Medicine ; R
Subject code	610
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Incidence and Characteristics of Kidney Stones in Patients on Ketogenic Diet

Prakrati Acharya / Chirag Acharya / Charat Thongprayoon / Panupong Hansrivijit / Swetha R. Kanduri / Karthik Kovvuru / Juan Medaura / Pradeep Vaitla / Desiree F. Garcia Anton / Poemlarp Mekraksakit / Pattharawin Pattharanitima / Tarun Bathini / Wisit Cheungpasitporn

Diseases, Vol 9, Iss 39, p

A Systematic Review and Meta-Analysis

2021 Volume 39

Abstract: Very-low-carbohydrate diets or ketogenic diets are frequently used for weight loss in adults and as a therapy for epilepsy in children. The incidence and characteristics of kidney stones in patients on ketogenic diets are not well studied. Methods: A ... ...

Abstract	Very-low-carbohydrate diets or ketogenic diets are frequently used for weight loss in adults and as a therapy for epilepsy in children. The incidence and characteristics of kidney stones in patients on ketogenic diets are not well studied. Methods: A systematic literature search was performed, using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from the databases’ inception through April 2020. Observational studies or clinical trials that provide data on the incidence and/or types of kidney stones in patients on ketogenic diets were included. We applied a random-effects model to estimate the incidence of kidney stones. Results: A total of 36 studies with 2795 patients on ketogenic diets were enrolled. The estimated pooled incidence of kidney stones was 5.9% (95% CI, 4.6–7.6%, I2 = 47%) in patients on ketogenic diets at a mean follow-up time of 3.7 +/− 2.9 years. Subgroup analyses demonstrated the estimated pooled incidence of kidney stones of 5.8% (95% CI, 4.4–7.5%, I2 = 49%) in children and 7.9% (95% CI, 2.8–20.1%, I2 = 29%) in adults, respectively. Within reported studies, 48.7% (95% CI, 33.2–64.6%) of kidney stones were uric stones, 36.5% (95% CI, 10.6–73.6%) were calcium-based (CaOx/CaP) stones, and 27.8% (95% CI, 12.1–51.9%) were mixed uric acid and calcium-based stones, respectively. Conclusions: The estimated incidence of kidney stones in patients on ketogenic diets is 5.9%. Its incidence is approximately 5.8% in children and 7.9% in adults. Uric acid stones are the most prevalent kidney stones in patients on ketogenic diets followed by calcium-based stones. These findings may impact the prevention and clinical management of kidney stones in patients on ketogenic diets.
Keywords	ketogenic diet ; kidney stones ; nephrolithiasis ; epidemiology ; meta-analysis ; systematic review ; Medicine ; R
Subject code	616
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Hospitalizations for Acute Salicylate Intoxication in the United States

Charat Thongprayoon / Tananchai Petnak / Wisit Kaewput / Michael A. Mao / Karthik Kovvuru / Swetha R. Kanduri / Boonphiphop Boonpheng / Tarun Bathini / Saraschandra Vallabhajosyula / Aleksandra I. Pivovarova / Himmat S. Brar / Juan Medaura / Wisit Cheungpasitporn

Journal of Clinical Medicine, Vol 9, Iss 2638, p

2020 Volume 2638

Abstract: Background: The objective of this study was to describe inpatient prevalence, characteristics, outcomes, and resource use for acute salicylate intoxication hospitalizations in the United States. Methods: A total of 13,805 admissions with a primary ... ...

Abstract	Background: The objective of this study was to describe inpatient prevalence, characteristics, outcomes, and resource use for acute salicylate intoxication hospitalizations in the United States. Methods: A total of 13,805 admissions with a primary diagnosis of salicylate intoxication from 2003 to 2014 in the National Inpatient Sample database were analyzed. Prognostic factors for in-hospital mortality were determined using multivariable logistic regression. Results: The overall inpatient prevalence of salicylate intoxication among hospitalized patients was 147.8 cases per 1,000,000 admissions in the United States. The average age was 34 ± 19 years. Of these, 35.0% were male and 65.4% used salicylate for suicidal attempts. Overall, 6% required renal replacement therapy. The most common complications of salicylate intoxication were electrolyte and acid-base disorders, including hypokalemia (25.4%), acidosis (19.1%), and alkalosis (11.1%). Kidney failure (9.3%) was the most common observed organ dysfunction. In-hospital mortality was 1.0%. Increased in-hospital mortality was associated with age ≥30, Asian/Pacific Islander race, diabetes mellitus, hyponatremia, ventricular arrhythmia, kidney failure, respiratory failure, and neurological failure, while decreased in-hospital mortality was associated with African American and Hispanic race. Conclusion: hospitalization for salicylate intoxication occurred in 148 per 1,000,000 admissions in the United States. Several factors were associated with in-hospital mortality.
Keywords	salicylate ; salicylate intoxication ; epidemiology ; hospitalization ; outcomes ; Medicine ; R
Subject code	310
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Incidence and Impacts of Inflammatory Bowel Diseases among Kidney Transplant Recipients

Panupong Hansrivijit / Max M. Puthenpura / Charat Thongprayoon / Himmat S. Brar / Tarun Bathini / Karthik Kovvuru / Swetha R. Kanduri / Karn Wijarnpreecha / Wisit Cheungpasitporn

Medical Sciences, Vol 8, Iss 39, p

A Meta-Analysis

2020 Volume 39

Abstract: Background: The incidence of inflammatory bowel diseases (IBD) and its significance in kidney transplant recipients is not well established. We conducted this systematic review and meta-analysis to assess the incidence of and complications from IBD in ... ...

Abstract	Background: The incidence of inflammatory bowel diseases (IBD) and its significance in kidney transplant recipients is not well established. We conducted this systematic review and meta-analysis to assess the incidence of and complications from IBD in adult kidney transplant recipients. Methods: Eligible articles were searched through Ovid MEDLINE, EMBASE, and the Cochrane Library from inception through April 2020. The inclusion criteria were adult kidney transplant patients with reported IBD. Effect estimates from the individual studies were extracted and combined using the fixed-effects model when I 2 ≤ 50% and random-effects model when I 2 > 50%. Results: of 641 citations, a total of seven studies ( n = 212) were included in the systematic review. The mean age was 46.2 +/− 6.9 years and up to 51.1% were male. The mean duration of follow-up was 57.8 +/− 16.8 months. The pooled incidence of recurrent IBD was 27.6% (95% CI, 17.7–40.5%; I 2 0%) while the pooled incidence of de novo IBD was 18.8% (95% CI, 10.7–31.0%; I 2 61.3%). The pooled incidence of post-transplant IBD was similar across subgroup analyses. Meta-regression analyses showed no association between the incidence of IBD and age, male sex, and follow-up duration. For post-transplant complications, the pooled incidence of post-transplant infection was 4.7% (95% CI, 0.5–33.3%; I 2 73.7%). The pooled incidence of graft rejection and re-transplantation in IBD patients was 31.4% (95% CI, 14.1–56.1%; I 2 76.9%) and 30.4% (95% CI, 22.6–39.5%; I 2 0%). Conclusion: Recurrent and de novo IBD is common among kidney transplant recipients and may result in adverse outcomes.
Keywords	inflammatory bowel diseases ; kidney transplantation ; meta-analysis ; systematic reviews ; Medicine ; R
Subject code	333
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Diagnostics, Risk Factors, Treatment and Outcomes of Acute Kidney Injury in a New Paradigm

Charat Thongprayoon / Panupong Hansrivijit / Karthik Kovvuru / Swetha R. Kanduri / Aldo Torres-Ortiz / Prakrati Acharya / Maria L. Gonzalez-Suarez / Wisit Kaewput / Tarun Bathini / Wisit Cheungpasitporn

Journal of Clinical Medicine, Vol 9, Iss 1104, p

2020 Volume 1104

Abstract: Acute kidney injury (AKI) is a common clinical condition among patients admitted in the hospitals. The condition is associated with both increased short-term and long-term mortality. With the development of a standardized definition for AKI and the ... ...

Abstract	Acute kidney injury (AKI) is a common clinical condition among patients admitted in the hospitals. The condition is associated with both increased short-term and long-term mortality. With the development of a standardized definition for AKI and the acknowledgment of the impact of AKI on patient outcomes, there has been increased recognition of AKI. Two advances from past decades, the usage of computer decision support and the discovery of AKI biomarkers, have the ability to advance the diagnostic method to and further management of AKI. The increasingly widespread use of electronic health records across hospitals has substantially increased the amount of data available to investigators and has shown promise in advancing AKI research. In addition, progress in the finding and validation of different forms of biomarkers of AKI within diversified clinical environments and has provided information and insight on testing, etiology and further prognosis of AKI, leading to future of precision and personalized approach to AKI management. In this this article, we discussed the changing paradigms in AKI: from mechanisms to diagnostics, risk factors, and management of AKI.
Keywords	acute kidney injury ; acute renal failure ; biomarkers ; critical care ; renal replacement therapy ; risk factors outcomes ; Medicine ; R
Subject code	610
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: SGLT2 Inhibitors and Kidney Outcomes in Patients with Chronic Kidney Disease

Swetha R. Kanduri / Karthik Kovvuru / Panupong Hansrivijit / Charat Thongprayoon / Saraschandra Vallabhajosyula / Aleksandra I. Pivovarova / Api Chewcharat / Vishnu Garla / Juan Medaura / Wisit Cheungpasitporn

Journal of Clinical Medicine, Vol 9, Iss 2723, p

2020 Volume 2723

Abstract: Globally, diabetes mellitus is a leading cause of kidney disease, with a critical percent of patients approaching end-stage kidney disease. In the current era, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as phenomenal agents in ... ...

Abstract	Globally, diabetes mellitus is a leading cause of kidney disease, with a critical percent of patients approaching end-stage kidney disease. In the current era, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as phenomenal agents in halting the progression of kidney disease. Positive effects of SGLT2i are centered on multiple mechanisms, including glycosuric effects, tubule—glomerular feedback, antioxidant, anti-fibrotic, natriuretic, and reduction in cortical hypoxia, alteration in energy metabolism. Concurrently, multiple kidney and cardiovascular outcome studies have reported remarkable advantages of SGLT2i including mortality benefits. Additionally, the superiority of combination therapies (SGLT2I along with metformin/DDP-4 Inhibitors) in treatment-naïve diabetic patients is further looked into with potential signal towards glycemic and blood pressure control. Reported promising results initiate a gateway for future research targeting kidney outcomes with combination therapies as an initial approach. In the current paper, we summarize leading cardiovascular and kidney outcome trials in patients with type 2 diabetes, the role of SGLT2i in non-diabetic proteinuric kidney disease, and the potential mechanisms of action of SGLT2i with special focus on combination therapy as an initial therapeutic approach in treatment-naïve diabetic patients.
Keywords	Diabetes mellitus ; SGLT2 ; SGLT2i ; sodium glucose co-transporter 2 inhibitors ; nephrology ; endocrinology ; Medicine ; R
Subject code	616 ; 610
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Treatment of C3 Glomerulopathy in Adult Kidney Transplant Recipients

Maria L Gonzalez Suarez / Charat Thongprayoon / Panupong Hansrivijit / Karthik Kovvuru / Swetha R Kanduri / Narothama R Aeddula / Aleksandra I Pivovarova / Api Chewcharat / Tarun Bathini / Michael A Mao / Arpita Basu / Wisit Cheungpasitporn

Medical Sciences, Vol 8, Iss 44, p

A Systematic Review

2020 Volume 44

Abstract: Background: C3 glomerulopathy (C3G), a rare glomerular disease mediated by alternative complement pathway dysregulation, is associated with a high rate of recurrence and graft loss after kidney transplantation (KTx). We aimed to assess the efficacy of ... ...

Abstract	Background: C3 glomerulopathy (C3G), a rare glomerular disease mediated by alternative complement pathway dysregulation, is associated with a high rate of recurrence and graft loss after kidney transplantation (KTx). We aimed to assess the efficacy of different treatments for C3G recurrence after KTx. Methods: Databases (MEDLINE, EMBASE, and Cochrane Database) were searched from inception through 3 May, 2019. Studies were included that reported outcomes of adult KTx recipients with C3G. Effect estimates from individual studies were combined using the random-effects, generic inverse variance method of DerSimonian and Laird., The protocol for this meta-analysis is registered with PROSPERO (no. CRD42019125718). Results: Twelve studies (7 cohort studies and 5 case series) consisting of 122 KTx patients with C3G (73 C3 glomerulonephritis (C3GN) and 49 dense deposit disease (DDD)) were included. The pooled estimated rates of allograft loss among KTx patients with C3G were 33% (95% CI: 12–57%) after eculizumab, 42% (95% CI: 2–89%) after therapeutic plasma exchange (TPE), and 81% (95% CI: 50–100%) after rituximab. Subgroup analysis based on type of C3G was performed. Pooled estimated rates of allograft loss in C3GN KTx patients were 22% (95% CI: 5–46%) after eculizumab, 56% (95% CI: 6–100%) after TPE, and 70% (95% CI: 24–100%) after rituximab. Pooled estimated rates of allograft loss in DDD KTx patients were 53% (95% CI: 0–100%) after eculizumab. Data on allograft loss in DDD after TPE (1 case series, 0/2 (0%) allograft loss at 6 months) and rituximab (1 cohort, 3/3 (100%) allograft loss) were limited. Among 66 patients (38 C3GN, 28 DDD) who received no treatment (due to stable allograft function at presentation and/or clinical judgment of physicians), pooled estimated rates of allograft loss were 32% (95% CI: 7–64%) and 53% (95% CI: 28–77%) for C3GN and DDD, respectively. Among treated C3G patients, data on soluble membrane attack complex of complement (sMAC) were limited to patients treated with eculizumab (N = 7). ...
Keywords	C3 glomerulopathy ; C3 glomerulonephritis ; dense deposit disease ; kidney transplantation ; renal transplantation ; Medicine ; R
Subject code	610
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Recent Advances and Clinical Outcomes of Kidney Transplantation

Charat Thongprayoon / Panupong Hansrivijit / Napat Leeaphorn / Prakrati Acharya / Aldo Torres-Ortiz / Wisit Kaewput / Karthik Kovvuru / Swetha R. Kanduri / Tarun Bathini / Wisit Cheungpasitporn

Journal of Clinical Medicine, Vol 9, Iss 1193, p

2020 Volume 1193

Abstract: Recent advances in surgical, immunosuppressive and monitoring protocols have led to the significant improvement of overall one-year kidney allograft outcomes. Nonetheless, there has not been a significant change in long-term kidney allograft outcomes. In ...

Abstract	Recent advances in surgical, immunosuppressive and monitoring protocols have led to the significant improvement of overall one-year kidney allograft outcomes. Nonetheless, there has not been a significant change in long-term kidney allograft outcomes. In fact, chronic and acute antibody-mediated rejection (ABMR) and non-immunological complications following kidney transplantation, including multiple incidences of primary kidney disease, as well as complications such as cardiovascular diseases, infections, and malignancy are the major factors that have contributed to the failure of kidney allografts. The use of molecular techniques to enhance histological diagnostics and noninvasive surveillance are what the latest studies in the field of clinical kidney transplant seem to mainly focus upon. Increasingly innovative approaches are being used to discover immunosuppressive methods to overcome critical sensitization, prevent the development of anti-human leukocyte antigen (HLA) antibodies, treat chronic active ABMR, and reduce non-immunological complications following kidney transplantation, such as the recurrence of primary kidney disease and other complications, such as cardiovascular diseases, infections, and malignancy. In the present era of utilizing electronic health records (EHRs), it is strongly believed that big data and artificial intelligence will reshape the research done on kidney transplantation in the near future. In addition, the utilization of telemedicine is increasing, providing benefits such as reaching out to kidney transplant patients in remote areas and helping to make scarce healthcare resources more accessible for kidney transplantation. In this article, we discuss the recent research developments in kidney transplants that may affect long-term allografts, as well as the survival of the patient. The latest developments in living kidney donation are also explored.
Keywords	kidney transplantation ; renal transplantation ; kidney transplant ; renal transplant ; transplant recipients ; transplantation ; Medicine ; R
Subject code	610
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Impact of ANCA-Associated Vasculitis on Outcomes of Hospitalizations for Goodpasture’s Syndrome in the United States

Charat Thongprayoon / Wisit Kaewput / Boonphiphop Boonpheng / Patompong Ungprasert / Tarun Bathini / Narat Srivali / Saraschandra Vallabhajosyula / Jorge L. Castaneda / Divya Monga / Swetha R. Kanduri / Juan Medaura / Wisit Cheungpasitporn

Medicina, Vol 56, Iss 3, p

Nationwide Inpatient Sample 2003–2014

2020 Volume 103

Abstract: Background and objectives : Goodpasture’s syndrome (GS) is a rare, life-threatening autoimmune disease. Although the coexistence of anti-neutrophil cytoplasmic antibody (ANCA) with Goodpasture’s syndrome has been recognized, the impacts of ANCA ... ...

Abstract	Background and objectives : Goodpasture’s syndrome (GS) is a rare, life-threatening autoimmune disease. Although the coexistence of anti-neutrophil cytoplasmic antibody (ANCA) with Goodpasture’s syndrome has been recognized, the impacts of ANCA vasculitis on mortality and resource utilization among patients with GS are unclear. Materials and Methods : We used the National Inpatient Sample to identify hospitalized patients with a principal diagnosis of GS from 2003 to 2014 in the database. The predictor of interest was the presence of ANCA-associated vasculitis. We tested the differences concerning in-hospital treatment and outcomes between GS patients with and without ANCA-associated vasculitis using logistic regression analysis with adjustment for other clinical characteristics. Results : A total of 964 patients were primarily admitted to hospital for GS. Of these, 84 (8.7%) had a concurrent diagnosis of ANCA-associated vasculitis. Hemoptysis was more prevalent in GS patients with ANCA-associated vasculitis. During hospitalization, GS patients with ANCA-associated required non-significantly more mechanical ventilation and non-invasive ventilation support, but non-significantly less renal replacement therapy and plasmapheresis than those with GS alone. There was no significant difference in in-hospital outcomes, including organ failure and mortality, between GS patients with and without ANCA-associated vasculitis. Conclusions : Our study demonstrated no significant differences between resource utilization and in-hospital mortality among hospitalized patients with coexistence of ANCA vasculitis and GS, compared to those with GS alone.
Keywords	goodpasture syndrome ; anca ; anti-gbm disease ; vasculitis ; hospitalization ; outcomes ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Promises of Big Data and Artificial Intelligence in Nephrology and Transplantation

Charat Thongprayoon / Wisit Kaewput / Karthik Kovvuru / Panupong Hansrivijit / Swetha R. Kanduri / Tarun Bathini / Api Chewcharat / Napat Leeaphorn / Maria L. Gonzalez-Suarez / Wisit Cheungpasitporn

Journal of Clinical Medicine, Vol 9, Iss 1107, p

2020 Volume 1107

Abstract: Kidney diseases form part of the major health burdens experienced all over the world. Kidney diseases are linked to high economic burden, deaths, and morbidity rates. The great importance of collecting a large quantity of health-related data among human ... ...

Abstract	Kidney diseases form part of the major health burdens experienced all over the world. Kidney diseases are linked to high economic burden, deaths, and morbidity rates. The great importance of collecting a large quantity of health-related data among human cohorts, what scholars refer to as “big data”, has increasingly been identified, with the establishment of a large group of cohorts and the usage of electronic health records (EHRs) in nephrology and transplantation. These data are valuable, and can potentially be utilized by researchers to advance knowledge in the field. Furthermore, progress in big data is stimulating the flourishing of artificial intelligence (AI), which is an excellent tool for handling, and subsequently processing, a great amount of data and may be applied to highlight more information on the effectiveness of medicine in kidney-related complications for the purpose of more precise phenotype and outcome prediction. In this article, we discuss the advances and challenges in big data, the use of EHRs and AI, with great emphasis on the usage of nephrology and transplantation.
Keywords	artificial intelligence ; machine learning ; big data ; nephrology ; transplantation ; kidney transplantation ; Medicine ; R
Subject code	020
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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