Sandeep K Mallipattu

• MD
• Professor (Associate) at Stony Brook University Hospital

Background Initial proximal tubule cell injury and dedifferentiation contribute to acute kidney injury (AKI), and persistent dedifferentiation drives fibrosis and chronic kidney disease (CKD). Proximal tubule-specific knockdown of zinc-finger transcription factor Krüppel-like factor 6 ( Klf6 ) attenuates the AKI to CKD transition. Our aim was to st...

Glomerular endothelial cell (GEnC) injury is a common feature across the wide spectrum of glomerular diseases. We recently reported that the endothelial-specific knockout of Krüppel-like factor 4 (Klf4) increases the susceptibility to GEnC injury and subsequent development of subacute thrombotic microangiopathy (TMA). However, the mechanism(s) medi...

Acute kidney injury (AKI) is a major risk factor for chronic kidney disease (CKD), and there are currently no therapies for AKI. Proximal tubules (PT) are particularly susceptible to AKI, including due to nephrotoxins such as aristolochic acid I (AAI). Normal PT utilize fatty acid oxidation and branched chain amino acid (BCAA; valine, leucine, isol...

Importance Understanding whether there are racial and ethnic and residential disparities in prenatal telehealth uptake is necessary for ensuring equitable access and guiding implementation of future hybrid (ie, both telehealth and in-person) prenatal care. Objective To assess temporal changes in individuals using hybrid prenatal care before and du...

Glomerular filtration rate (GFR) is the main functional index of kidney health and disease. Currently, no methods are available to directly measure tubular mass and function. Here, we report a serendipitous finding that the in vitro cell viability dye resazurin can be used in mice as an exogenous sensor of tubular function. Intravenously injected r...

Diabetic kidney disease (DKD) is the main cause of chronic kidney disease worldwide. While injury to the podocytes, visceral epithelial cells that comprise the glomerular filtration barrier, drives albuminuria, proximal tubule (PT) dysfunction is the critical mediator of DKD progression. Here, we report that the podocyte-specific induction of human...

Background Podocyte loss is the major driver of primary glomerular diseases such as Focal Segmental Glomerulosclerosis. While systemic glucocorticoids remain the initial and primary therapy for these diseases, high-dose and chronic use of glucocorticoids is riddled with systemic toxicities. Krüppel-Like Factor 15 (KLF15) is a glucocorticoid-respons...

Podocytes are highly specialized epithelial cells that surround the capillaries of the glomeruli in the kidney. Together with the glomerular endothelial cells, these post-mitotic cells are responsible for regulating filtrate from the circulating blood with their organized network of interdigitating foot processes that wrap around the glomerular bas...

Profilin1 belongs to a family of small monomeric actin-binding proteins with diverse roles in fundamental actin-dependent cellular processes required for cell survival. Podocytes are postmitotic visceral epithelial cells critical for the structure and function of the kidney filtration barrier. There is emerging evidence that the actin-related mode...

Introduction: Endotoxin is a key driver of sepsis, which frequently causes acute kidney injury (AKI). However, endotoxins may also be found in non-bacteremic critically ill patients, likely from intestinal translocation. Preclinical models show that endotoxins can directly injure the kidneys, and in COVID-19 patients, endotoxemia correlated with A...

The COVID-19 pandemic resulted in an unprecedented burden on intensive care units (ICUs). With increased demands and limited supply, critical care resources, including dialysis machines, became scarce, leading to the undertaking of value-based cost-effectiveness analyses and the rationing of resources to deliver patient care of the highest quality....

Objective The effects of Coronavirus disease 2019 (COVID-19) infection and altered processes of care on nonelective coronary artery bypass grafting (CABG) outcomes remain unknown. We hypothesized that patients with COVID-19 infection would have longer hospital lengths of stay and greater mortality compared with COVID-negative patients, but that the...

High-multiplex detection of protein biomarkers across tissue regions has been an attractive spatial biology approach due to significant advantages over traditional immunohistochemistry (IHC) methods. Different from most methods, spatial multiplex in situ tagging (MIST) transfers the spatial protein expression information to an ultrahigh-density, la...

Objectives To define pregnancy episodes and estimate gestational age within electronic health record (EHR) data from the National COVID Cohort Collaborative (N3C). Materials and Methods We developed a comprehensive approach, named Hierarchy and rule-based pregnancy episode Inference integrated with Pregnancy Progression Signatures (HIPPS), and app...

Background: Acute kidney injury (AKI) is associated with mortality in patients hospitalized with COVID-19, however, its incidence, geographic distribution, and temporal trends since the start of the pandemic are understudied. Methods: Electronic health record data were obtained from 53 health systems in the United States (US) in the National COV...

Exogenous estrogen is associated with reduced COVID mortality in non-immunosuppressed/immunocompromised (non-ISC) post-menopausal females. Here, we examined the association of estrogen or testosterone hormone replacement therapy (HRT) with COVID outcomes in solid organ transplant recipients (SOTR) compared to non-ISC individuals, given known differ...

Podocytes and parietal epithelial cells (PECs) are among the few principal cell types within the kidney glomerulus, the former serving as a crucial constituent of the kidney filtration barrier and the latter representing a supporting epithelial layer that adorns the inner wall of Bowman's capsule. Podocytes and PECs share a circumscript development...

Lip‐reading provides an effective speech communication interface for people with voice disorders and for intuitive human–machine interactions. Existing systems are generally challenged by bulkiness, obtrusiveness, and poor robustness against environmental interferences. The lack of a truly natural and unobtrusive system for converting lip movements...

Introduction: Fibroblast growth factor (FGF) 23 is strongly upregulated in end-stage renal disease (ESRD) on dialysis and induces left ventricular hypertrophy (LVH) through activation of cardiac FGF receptor 4. Recent experimental animal data suggest that heparin acts as a co-receptor for FGF23, promoting binding to cardiac cells and LVH. Hypothesi...

The kidney, and in particular the proximal tubule (PT), has a high demand for ATP, due to its function in bulk reabsorption of solutes. In normal PT, ATP levels are predominantly maintained by fatty acid β-oxidation (FAO), the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation. The normal PT also undertakes gluconeogenesis and metabolism...

Background: Acute kidney injury (AKI) is associated with mortality in patients hospitalized with COVID-19, however, its incidence, geographic distribution, and temporal trends since the start of the pandemic are understudied. Methods: Electronic health record data were obtained from 53 health systems in the United States (US) in the National COVID...

Thrombotic microangiopathy (TMA) in the kidney represents the most severe manifestation of kidney microvascular endothelial injury. Despite the source of the inciting event, the diverse clinical forms of kidney TMA share dysregulation of endothelial cell transcripts and complement activation. Here, we show that endothelial-specific knockdown of Krü...

Background: Severe AKI is strongly associated with poor outcomes in coronavirus disease 2019 (COVID-19), but data on renal recovery are lacking. Methods: We retrospectively analyzed these associations in 3299 hospitalized patients (1338 with COVID-19 and 1961 with acute respiratory illness but who tested negative for COVID-19). Uni- and multivar...

Kidney disease is an epidemic that affects more than 600 million people worldwide. The socioeconomic impacts of the disease disproportionately affect Hispanic and non-Hispanic Black Americans, making the disease an issue of social inequality. The urgency of this situation has only become worse during the COVID-19 pandemic, as those who are hospital...

Increased oxidative stress in glomerular endothelial cells (GEnCs) contributes to early diabetic kidney disease (DKD). While mitochondrial respiratory complex IV activity is reduced in DKD, it remains unclear whether this is a driver or a consequence of oxidative stress in GEnCs. Synthesis of cytochrome C oxidase 2 (SCO2), a key metallochaperone in...

Loss of fatty acid β-oxidation (FAO) in the proximal tubule is a critical mediator of acute kidney injury and eventual fibrosis. However, transcriptional mediators of FAO in proximal tubule injury remain understudied. Krüppel-like factor 15 (KLF15), a highly enriched zinc-finger transcription factor in the proximal tubule , was significantly reduce...

Podocyte loss triggering aberrant activation and proliferation of parietal epithelial cells (PECs) is a central pathogenic event in proliferative glomerulopathies. Podocyte-specific Krüppel-like factor 4 (KLF4), a zinc-finger transcription factor, is essential for maintaining podocyte homeostasis and PEC quiescence. Using mice with podocyte-specifi...

Introduction: Mechanism(s) mediating critical illness in coronavirus disease 2019 (COVID-19) remain unclear. Previous reports demonstrate the existence of endotoxemia in viral infections without superimposed gram-negative bacteremia, but the rate and severity of endotoxemia in critically ill patients with COVID-19 requires further exploration. Ma...

Importance The National COVID Cohort Collaborative (N3C) is a centralized, harmonized, high-granularity electronic health record repository that is the largest, most representative COVID-19 cohort to date. This multicenter data set can support robust evidence-based development of predictive and diagnostic tools and inform clinical care and policy....

Significance The kidney proximal tubule is particularly susceptible to acute injury, which results in loss of fatty acid oxidation (FAO), their primary energy source. Here, we show that loss of the transcription factor KLF6 specifically in the proximal tubule in mice protects against acute injury and fibrosis, with preservation of transcripts that...

Background: The majority of U.S. reports of COVID-19 clinical characteristics, disease course, and treatments are from single health systems or focused on one domain. Here we report the creation of the National COVID Cohort Collaborative (N3C), a centralized, harmonized, high-granularity electronic health record repository that is the largest, most...

Background Retrospective studies on the use of Renin-Angiotensin-Aldosterone System blockade in patients with Coronavirus Disease 2019 (COVID-19) have been informative but conflicting, and prospective studies are required to demonstrate the safety, tolerability, and outcomes of initiating these agents in hospitalized patients with COVID-19 and hype...

Mitochondria play a complex role in maintaining cellular function including ATP generation, generation of biosynthetic precursors for macromolecules, maintenance of redox homeostasis, and metabolic waste management. Although the contribution of mitochondrial function in various kidney diseases has been studied, there are still avenues that need to...

Introduction: Acute kidney injury (AKI) is strongly associated with poor outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19), but data on the association of proteinuria and hematuria are limited to non-US populations. In addition, admission and in-hospital measures for kidney abnormalities have not been studied separately....

Background: The global coronavirus disease 2019 (COVID-19) pandemic offers the opportunity to assess how hospitals manage the care of hospitalized patients with varying demographics and clinical presentations. The goal of this study was to demonstrate the impact of densely populated residential areas on hospitalization and to identify predictors o...

Background This study investigated continued and discontinued use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) during hospitalization of 614 hypertensive laboratory-confirmed COVID-19 patients. Methods Demographics, comorbidities, vital signs, laboratory data, and ACEi/ARB usage were analyzed. To acc...

The proximal tubule (PT) is a major target in acute kidney injury (AKI), leading to profound changes in PT cell biology. Amongst the genes with early and robust changes in expression are many transcription factors (TFs), which themselves account for other transcriptomic changes. Potentially important TFs are being revealed in large sequencing datas...

There is a well-established, yet unexplained high prevalence of cardiovascular morbidity and mortality in individuals with End Stage Kidney Disease on dialysis. Potential etiologies include changes in cardiac structure and function, with increased left ventricular mass index as the best established cardiac structural change associated with this inc...

Background Data regarding the benefits or harm associated with the continuation of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), especially the effect on inflammation, in patients who are hypertensive and hospitalized with coronavirus disease 2019 (COVID-19) in the United States are unclear. Methods...

Background Thrombotic microangiopathy (TMA) represents the most severe manifestation of glomerular endothelial injury consisting of endothelial cell (EC) swelling, subendothelial expansion, inflammation and microthrombi. TMA occurs subsequent to various etiologies and is associated with dysregulation of thrombotic and inflammatory transcripts and c...

Diabetic Kidney Disease (DKD) is an important public health problem. Podocyte injury is a central event in the mechanism of DKD development. Podocytes are terminally differentiated, highly specialized glomerular visceral epithelial cells critical for the maintenance of the glomerular filtration barrier. Although potential mechanisms by which diabet...

Acute heart failure exacerbations center around volume overload and treatment of this disease process often requires aggressive diuresis in order to achieve symptomatic relief. The management of heart failure through the use of intravenous diuretics is at times limited due to renal function. An elevated Cr level, which has previously been associate...

The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway is a multifaceted transduction system which regulates cellular responses to incoming signaling ligands. Signal transducer and activator of transcription 3 (STAT3) is a central member of the JAK/STAT signaling cascade and has long been recognized for its...

Podocyte injury contributing to parietal epithelial cell (PEC) proliferation is a dominant histologic feature in both rapidly progressive glomerulonephritis (RPGN) and subtypes of focal segmental glomerulosclerosis (FSGS). Activation of Signal Transducer and Activator of Transcription 3 (STAT3) signaling is critical to the progression of both. We r...

Inhibition of vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling is a common therapeutic strategy in oncology, with new drugs continuously in development. In this review, we consider the experimental and clinical evidence behind the diverse nephrotoxicities associated with the inhibition of...

Background: Podocyte injury is the hallmark of proteinuric kidney diseases, such as FSGS and minimal change disease, and destabilization of the podocyte's actin cytoskeleton contributes to podocyte dysfunction in many of these conditions. Although agents, such as glucocorticoids and cyclosporin, stabilize the actin cytoskeleton, systemic toxicity...

Mitochondrial injury is uniformly observed in several murine models as well as in individuals with diabetic kidney disease (DKD). Although emerging evidence has highlighted the role of key transcriptional regulators in mitochondrial biogenesis, little is known about the regulation of mitochondrial cytochrome c oxidase (COX) assembly in the podocyte...

Pathologic glomerular epithelial cell (GEC) hyperplasia is characteristic of both rapidly progressive glomerulonephritis (RPGN) and subtypes of focal segmental glomerulosclerosis (FSGS). Although initial podocyte injury resulting in activation of STAT3 signals GEC proliferation in both diseases, mechanisms regulating this are unknown. Here, we show...

Large epidemiological studies clearly demonstrate that multiple episodes of acute kidney injury contribute to the development and progression of kidney fibrosis. Although our understanding of kidney fibrosis has improved in the past two decades, we have limited therapeutic strategies to halt its progression. Myofibroblast differentiation and prolif...

Krüppel-like factors (KLFs) are a family of zinc-finger transcription factors that are found in many species. Recent studies have shown that KLFs play a fundamental role in regulating diverse biological processes such as cell proliferation, differentiation, development and regeneration. Of note, several KLFs are also crucial for maintaining pluripo...

The etiology of renal insufficiency includes primary (e.g., polycystic kidney disease) or secondary (e.g., contrast media, diabetes) causes. The regulatory restrictions placed on the use of contrast agents (CAs) for noninvasive imaging modalities such as X-ray computed tomography (CT) and magnetic resonance imaging (MRI) affect the clinical managem...

Krüppel-like factors (KLFs) are a family of zinc-finger transcription factors critical to mammalian embryonic development, regeneration, and human disease. There is emerging evidence that KLFs play a vital role in key physiological processes in the kidney, ranging from maintenance of glomerular filtration barrier to tubulointerstitial inflammation...

Podocyte injury is the inciting event in primary glomerulopathies, such as minimal change disease and primary FSGS, and glucocorticoids remain the initial and often, the primary treatment of choice for these glomerulopathies. Because inflammation is not readily apparent in these diseases, understanding the direct effects of glucocorticoids on the p...

Loss of functional nephrons induces compensatory glomerular hyperfiltration and hypertrophy, leading to the progression of chronic kidney disease. Krüppel-like factor 2 (KLF2), a shear-stress-inducible transcription factor, confers protection against endothelial injury. Because glomerular hyperfiltration is associated with shear stress, we hypothes...

The Centers for Disease Control and Prevention estimates more than 10% of adults in the United States, over 20 million Americans have chronic kidney disease (CKD). A failure to maintain the glomerular filtration barrier directly contributes to the onset of CKD. The visceral epithelial cells, podocytes, are integral to the maintenance of this renal...

No abstract is available for this article.

The primary etiology of chronic kidney disease is a direct consequence of initial glomerular dysfunction. Podocytes (visceral glomerular epithelial cells) in normal mature kidneys are regarded as highly differentiated and quiescent cells. Krüppel‐like factors (KLFs), zinc‐finger DNA‐binding transcription factors, play a critical role in podocyte bi...