Shuchita Sharma - Academia.edu (original) (raw)

Papers by Shuchita Sharma

Research paper thumbnail of Home Dialysis: A Majority Chooses It, a Minority Gets It

Blood Purification, 2021

Introduction: When choosing a modality for outpatient renal replacement therapy, patients and med... more Introduction: When choosing a modality for outpatient renal replacement therapy, patients and medical providers have 3 options to choose from in-center hemodialysis (HD), home HD (HHD), and peritoneal dialysis (PD). In 2017, just over 10% of incident ESKD patients were on a home dialysis modality. We set out to determine outcomes of dialysis modality education in both pre-dialysis and dialysis patients. Moreover, we examined barriers that preclude patients from choosing home dialysis. Methods: This was a single-center, retrospective study looking at patients who were referred to the CKD educator for dialysis modality education between January 1, 2019, and March 31, 2020. Patient demographics, preferred language of communication, stage of renal disease, and reasons for patients’ refusal to undertake a home dialysis modality were recorded. Patients’ average household income and driving distance to our home dialysis unit were calculated using their home zip code. Results: 167 patients ...

Research paper thumbnail of Telenephrology with Remote Peritoneal Dialysis Monitoring during Coronavirus Disease 19

American Journal of Nephrology, 2020

Research paper thumbnail of Acute Start Peritoneal Dialysis during the COVID-19 Pandemic: Outcomes and Experiences

Journal of the American Society of Nephrology, 2020

Research paper thumbnail of Outcomes of Patients on Maintenance Dialysis Hospitalized with COVID-19

Clinical Journal of the American Society of Nephrology, 2020

Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-... more Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had devastating effects worldwide. Patients with kidney failure on dialysis may have a higher risk of worse outcomes. Reports from China found that these patients with SARS-CoV-2 had fewer symptoms and required less intensive care than expected (1). A recent observational study of hospitalized patients with kidney failure and COVID-19 reported 31% mortality (2). However, this study lacked a comparator group, and thus, it is unclear if this high mortality would be found in patients without kidney failure with a similarly high comorbidity burden. Therefore, we conducted this retrospective cohort study of patients with kidney failure hospitalized with COVID-19 in the Mount Sinai Health Care System (MSHS) and compared it with a propensity-matched cohort without kidney failure. Only patients age $18 years admitted between March 15 and June 7, 2020, with laboratoryconfirmed SARS-CoV-2 within 48 hours of admission were included. Patients with kidney failure were identified by a combination of kidney failure diagnosis and dialysis procedure International Classificaton of Diseases codes. Patients with previous kidney transplants were not excluded if they had kidney failure at the time of study. The Mount Sinai Institutional Review Board approved this research. We propensity matched patients with kidney failure to those without kidney failure (1:5) without use of a caliper by age, sex, race/ethnicity, comorbidities (atrial fibrillation, coronary artery disease, cancer, congestive heart failure, diabetes, hypertension, chronic obstructive pulmonary disease, asthma, peripheral vascular disease, stroke, and liver disease), body mass index (kilograms per meter 2), admission facility, and admission week using nearest neighbor matching. Despite propensity matching, significant differences in patient characteristics remained between kidney failure and non-kidney failure cohorts. Therefore, we performed logistic regression analysis after controlling for age, diabetes, hypertension, stroke, coronary artery disease, and congestive heart failure to determine the association between kidney failure and mechanical ventilation, intensive care unit (ICU) admission, and

Research paper thumbnail of COVID-19–Associated Acute Kidney Injury and Quantified Protein Catabolic Rate: A Likely Effect of Cytokine Storm on Muscle Protein Breakdown

Kidney Medicine, 2021

Previously we reported a cohort of patients with coronavirus disease 2019 (COVID-19)-associated a... more Previously we reported a cohort of patients with coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) with striking biochemical evidence of tissue breakdown in the absence of apparent rhabdomyolysis. We sought to quantify the extent of tissue catabolism in similar patients. Study Design: During acute peritoneal dialysis (PD) in patients with COVID-19-associated AKI, we measured urea Kt/V adequacy and calculated the daily urea nitrogen generation rate while quantifying daily protein intake.

Research paper thumbnail of Bilateral Renal Artery Thrombosis in a Patient With COVID-19

Kidney Medicine, 2020

Reports of the incidence of acute kidney injury in patients with coronavirus disease 2019 (COVID-... more Reports of the incidence of acute kidney injury in patients with coronavirus disease 2019 (COVID-19) have varied greatly from 0.5% to as high as 39%, with onset generally within 7 days from time of admission. The nature of the kidney insult is acute tubular necrosis, immune cell infiltration, or rhabdomyolysis, as demonstrated in autopsy reports. Moreover, infection with COVID-19 has been associated with coagulation abnormalities, as well as complement-mediated generalized thrombotic microvascular injury. These patients have been found to have high D-dimer, fibrin degradation product, and fibrinogen values, an elevated international normalized ratio, normal partial thromboplastin time, and normal platelet count values. Renal artery thrombosis is a rare condition, the most common cause of which is atrial fibrillation. However, bilateral completely occlusive renal artery thrombosis is even rarer. We present a case of a patient with COVID-19 on systemic anticoagulation therapy who presented with a serum creatinine level of 6.04 mg/dL requiring the initiation of kidney replacement therapy and was found to have bilateral renal artery thrombosis.

Research paper thumbnail of Home Dialysis Training for Fellows: Privilege or Necessity?

American Journal of Kidney Diseases, 2020

T here is a great discrepancy between the modality that nephrologists would choose if they themse... more T here is a great discrepancy between the modality that nephrologists would choose if they themselves were to start dialysis and the reality of the current dialysis situation in the United States. In a 2010 survey reported by Merighi et al, 1 629 practicing US nephrologists were asked "If your kidneys failed and there was a 5-year wait for a transplant, which type of dialysis would you choose?" Only 6% chose in-center hemodialysis (HD); by contrast, of the prevalent dialysis population in that same year, 92% were receiving incenter HD. One would be pressed to find another situation for which there is such a stark difference between physicians' and patients' choices. This suggests that nephrologists are aware of benefits associated with home dialysis and would choose home dialysis for themselves, but other factors, both medical and nonmedical, have an important role in determining the dialysis modality that patients receive. Patient factors include comorbid conditions, psychosocial and financial barriers, and patient and partner education about home dialysis. 2 Provider factors, as noted in a recent NKF-KDOQI conference outcomes report, 2 include a lack of education and perceived competence in prescribing home dialysis. This should come as little surprise. Although the number of kidney replacement therapy (KRT) patients in the United States continues to grow, increasing from 304,420 in 1996 to 726,331 in 2016, 3 KRT modality choice continues to be lopsided, with 87.5% of incident patients with kidney failure in 2016 receiving HD, 9.7% receiving peritoneal dialysis (PD), and only 2.8% receiving a kidney transplant. 3 Of patients who initiated HD, only 2% started with home HD (HHD), whereas an overwhelming 98% started with in-center dialysis. Among prevalent dialysis patients, numbers are similar, with 87.6% receiving in-center HD; 1.8%, HHD; and 10.1%, PD. 3 This low prevalence leads to a lack of exposure to home therapies among US nephrologists, thereby reducing expertise and comfort in prescribing and caring for home dialysis patients. 4

Research paper thumbnail of Acute Kidney Injury In Hospitalized Patients Who Underwent Percutaneous Kidney Biopsy

Background Performing a kidney biopsy is necessary to accurately diagnose diseases such as glomer... more Background Performing a kidney biopsy is necessary to accurately diagnose diseases such as glomerulonephritis and tubulointerstitial nephritis, among other such conditions. These conditions predispose patients to chronic kidney disease, as well as acute kidney injury (AKI). Notably, most epidemiological studies describing AKI have not investigated this patient population. Methods Included patients admitted to the nephrology ward of a tertiary hospital who underwent percutaneous kidney biopsy. AKI was diagnosed based on the Kidney Disease: Improving Global Outcomes criteria. Results Of the 223 patients investigated, 140 (62.8%) showed AKI. Of these, 91 (65%), 19 (13.6%), and 30 (21.4%) presented with AKI classified as stages 1, 2, and 3, respectively. The primary indication for performing biopsy was nephrotic syndrome or nephrotic proteinuria (73 [52.1%] in the AKI vs. 51 [61.4%] in the non-AKI group, p=0.048). Focal segmental glomerulosclerosis was the most prevalent primary disease...

Research paper thumbnail of Retinoic acid improves nephrotoxic serum-induced glomerulonephritis through activation of podocyte retinoic acid receptor α

Kidney international, Dec 27, 2017

Proliferation of glomerular epithelial cells, including podocytes, is a key histologic feature of... more Proliferation of glomerular epithelial cells, including podocytes, is a key histologic feature of crescentic glomerulonephritis. We previously found that retinoic acid (RA) inhibits proliferation and induces differentiation of podocytes by activating RA receptor-α (RARα) in a murine model of HIV-associated nephropathy. Here, we examined whether RA would similarly protect podocytes against nephrotoxic serum-induced crescentic glomerulonephritis and whether this effect was mediated by podocyte RARα. RA treatment markedly improved renal function and reduced the number of crescentic lesions in nephritic wild-type mice, while this protection was largely lost in mice with podocyte-specific ablation of Rara (Pod-Rara knockout). At a cellular level, RA significantly restored the expression of podocyte differentiation markers in nephritic wild-type mice, but not in nephritic Pod-Rara knockout mice. Furthermore, RA suppressed the expression of cell injury, proliferation, and parietal epitheli...

Research paper thumbnail of Hypertension in Pregnancy

Cardiology in Review, 2010

ABSTRACT

Research paper thumbnail of Hemodialysis venous needle dislodgement to the heart: a case report

The Journal of Vascular Access, 2012

Research paper thumbnail of Hemodialysis venous needle dislodgement to the heart: a case report

The Journal of Vascular Access, 2012

Research paper thumbnail of A comparison of podocyturia, albuminuria and nephrinuria in predicting the development of preeclampsia: a prospective study

PloS one, 2014

Preeclampsia, a hypertensive multisystem disease that complicates 5-8% of all pregnancy, is a maj... more Preeclampsia, a hypertensive multisystem disease that complicates 5-8% of all pregnancy, is a major cause for maternal and fetal mortality and morbidity. The disease is associated with increased spontaneous and evoked preterm birth and remote cardio-renal disorders in the mother and offspring. Thus the ability to predict the disease should lead to earlier care and decreased morbidity. This has led to fervent attempts to identify early predictive biomarkers and research endeavors that have expanded as we learn more regarding possible causes of the disease. As preeclampsia is associated with specific renal pathology including podocyte injury, early urinary podocyte (podocyturia), or the podocyte specific proteinuria nephrin in the urine (nephrinuria), as well as the more easily measured urinary albumin (albuminuria), have all been suggested as predictive markers. We performed a prospective study recruiting 91 pregnant women (78 of whom were high risk) and studied the predictive abilit...

Research paper thumbnail of Expression of Notch pathway proteins correlates with albuminuria, glomerulosclerosis, and renal function

Kidney International, 2010

Recent studies indicate that the Notch signaling pathway plays an important role in the developme... more Recent studies indicate that the Notch signaling pathway plays an important role in the development of diabetic kidney disease and focal segmental glomerulosclerosis (FSGS). Here we analyzed the degree of expression and localization of Notch ligands (Jagged1 and Delta1) and activated (cleaved) receptors (Notch1 and Notch2) in healthy human kidneys and in renal biopsies from a wide variety of kidney diseases. These included patients with minimal change disease, membranous nephropathy, lupus nephritis ISN/RPS classes III/IV/V, hypertensive nephrosclerosis, crescentic glomerulonephritis, tubulointerstitial fibrosis, IgA nephropathy, diabetic kidney disease, and FSGS. We found that cleaved Notch1, Notch2, and Jagged1 are expressed on podocytes in proteinuric nephropathies and their level of expression correlated with the amount of proteinuria across all disease groups. The degree of glomerulosclerosis correlated with podocyte expression of cleaved Notch1, while the severity of tubulointerstitial fibrosis and the estimated glomerular filtration rate correlated with expression of cleaved Notch1 in the tubulointerstitium. Hence, our results raise the possibility that Notch pathway activation is a common mechanism in the pathophysiology of a wide range of acquired renal diseases.

Research paper thumbnail of The story of Notch and chronic kidney disease

Current Opinion in Nephrology and Hypertension, 2011

Purpose of the review-The Notch pathway is an evolutionary conserved cell-cell communication mech... more Purpose of the review-The Notch pathway is an evolutionary conserved cell-cell communication mechanism that plays a key role in kidney development. Here we will discuss a number of recently published papers describing the role of Notch signaling in kidney development, homeostasis, injury and repair. Recent findings-Recent gene expression studies identified regulation of the Notch pathway in patients with chronic kidney disease (CKD). Mechanistic experiments performed using transgenic and knockout mouse models indicate that Notch plays an important functional role in the development of proteinuria and renal fibrosis. Inhibition of the Notch pathway ameliorated diabetic kidney disease, nephrotic syndrome and fibrosis in different rodent models. Summary-An increasing amount of evidence suggests that Notch plays a role in CKD development. Understanding the role of Notch signaling in the kidney can aid in the development of new therapeutics for CKD.

Research paper thumbnail of 151: Intradialytic Use of Heparin: Is Heparin Necessary for Stable Chronic Hemodialysis Treatments?

American Journal of Kidney Diseases, 2010

Diuretics are thought to contribute to deterioration of renal function in patients with heart fai... more Diuretics are thought to contribute to deterioration of renal function in patients with heart failure (HF). Renal dysfunction and hyponatremia are both known to be associated with increased morbidity and mortality in these patients. Vasopressin receptor antagonists (VRA) and Adenosine-A1 receptor antagonists (A1RA) represent emerging pharmacological therapies that potentially lack the renal adverse effects of diuretics. This study explores the currently available data on the impact of these agents on kidney-related parameters. Articles cited in PubMed database from 1980 to 2009 using key words: "vasopressin receptor antagonist", "ADH-receptor antagonist", Adenosine-A1 receptor Antagonists", and "heart failure" were searched. Those clinical randomized controlled trials that exclusively included HF population were identified, and relevant articles were selected. The results of these studies were then reviewed and compared with regards to kidneyrelated parameters. A total of 27 and 22 relevant articles were identified for VRA and A1RA respectively. Nine randomized, placebo-controlled trials were selected to be included in this study for VRA, and 6 for A1RA. For VRA, 4 studies (44.5%) could not find any significant change in serum sodium levels, and the rest showed only a modest rise (e.g.≤4meq/l). Seven studies (77.8%) did not find any significant change in renal function. For A1RA, 3 studies (50%) did not show any significant change in renal function, and only two studies (33%) found increase in urine volume. While there is a promising theoretical basis and possible cardiac benefits for use of VRA and A1RA as adjunct therapy for patients with HF, currently available data show only modest beneficial impact on kidney-related parameters for both therapies. Future large-sized trials are clearly needed to further evaluate these effects and their potential impact on morbidity and mortality of patients with HF.

Research paper thumbnail of Urinary Albumin vs. Urinary Nephrin in Predicting the Development of Preeclampsia

American Journal of Kidney Diseases, 2012

Despite the high prevalence of preeclampsia, the ability to predict its occurrence is still probl... more Despite the high prevalence of preeclampsia, the ability to predict its occurrence is still problematic. There is evidence that alterations in the podocyte, a specialized visceral epithelial cell that lines the glomerular filtration barrier, may be linked to the pathogenesis of preeclampsia. We proposed to study whether markers of podocyte injury, in the form of urinary albumin and urinary nephrin, would be predictive of preeclampsia when measured early in pregnancy in obstetric patients who are at high risk of developing complications. We conducted a prospective study on 67 high risk obstetric patients (chronic hypertension, diabetes mellitus of any type, chronic kidney disease, SLE) and 14 healthy control obstetric patients in their 2 nd and 3 rd trimester of gestation. During the subjects' clinic visit, a 20 ml of urine sample was analyzed for random urine albumin and urine creatinine concentration using standard laboratory techniques. Urine nephrin concentration was measured using an enzyme-linked immunosorbent assay (Exocell Inc., Philadelphia, PA). Urine albumin-creatinine ratio (UACR) and urine nephrin-to-creatinine ratio (UNCR) were determined to control for the concentration of the urine. These subjects were followed until delivery. Unpaired parametric t-test analysis revealed that UACR in the 2 nd and 3 rd trimester were significantly higher for patients who developed preeclampsia as compared with those who didn't (p=0.04 and p=0.006 respectively). Similarly, UNCR in the 2 nd and 3 rd trimester also showed significantly higher levels (p=0.01 and p=0.004 respectively). When 2 nd and 3 rd trimester patients were combined, both UACR and UNCR continued to demonstrate significant differences between these two patients groups (p=0.01 and p=0.0005 respectively). We conclude that both UACR and UNCR are predictive of the development of preeclampsia when measured as early as the 2 nd trimester in pregnancy.

Research paper thumbnail of The Association between Prevalence of Peritoneal Dialysis versus Hemodialysis and Patients’ Distance to Dialysis-Providing Facilities

Kidney360, 2021

BackgroundAccessibility to dialysis facilities plays a central role when deciding on a patient’s ... more BackgroundAccessibility to dialysis facilities plays a central role when deciding on a patient’s long-term dialysis modality. Studies investigating the effect of distance to nearest dialysis-providing unit on modality choice have yielded conflicting results. We set out to investigate the association between patients’ dialysis modality and both the driving and straight-line distances to the closest HD- and PD-providing units.MethodsAll patients with ESKD who initiated in-center HD and PD in 2017, were 18–90 years old, and were on dialysis for ≥30 days were included. Patients in residence zip codes in nonconterminous United States or lived >90 miles from the nearest HD-providing unit were excluded.ResultsA total of 102,247 patients in the United States initiated in-center HD and PD in 2017. Compared with patients on HD, patients on PD had longer driving distances to their nearest PD unit (4.4 versus 3.4 miles; P<0.001). Patients who lived >30 miles from the nearest HD unit we...

Research paper thumbnail of The Association between Prevalence of Peritoneal Dialysis versus Hemodialysis and Patients’ Distance to Dialysis-Providing Facilities

Kidney360, 2021

BackgroundAccessibility to dialysis facilities plays a central role when deciding on a patient’s ... more BackgroundAccessibility to dialysis facilities plays a central role when deciding on a patient’s long-term dialysis modality. Studies investigating the effect of distance to nearest dialysis-providing unit on modality choice have yielded conflicting results. We set out to investigate the association between patients’ dialysis modality and both the driving and straight-line distances to the closest HD- and PD-providing units.MethodsAll patients with ESKD who initiated in-center HD and PD in 2017, were 18–90 years old, and were on dialysis for ≥30 days were included. Patients in residence zip codes in nonconterminous United States or lived >90 miles from the nearest HD-providing unit were excluded.ResultsA total of 102,247 patients in the United States initiated in-center HD and PD in 2017. Compared with patients on HD, patients on PD had longer driving distances to their nearest PD unit (4.4 versus 3.4 miles; P<0.001). Patients who lived >30 miles from the nearest HD unit we...

Research paper thumbnail of 281: Urinary Excretion of Podocytes as an Early Marker of Diabetic Nephropathy

American Journal of Kidney Diseases, 2010

Pathogenesis of diabetic nephropathy (DN) is related to podocyte injury and loss. Podocytes, whic... more Pathogenesis of diabetic nephropathy (DN) is related to podocyte injury and loss. Podocytes, which are located on the outer surface of the glomerular basement membrane, appear in the urine as a result of detachment. Microalbuminuria has been traditionally used to detect the onset of DN; its appearance usually prompts aggressive treatment. The aim of this study is to determine whether the podocytes are lost in diabetic patients even before the appearance of microalbuminuria, and that it may serve as an earlier marker of DN. Twelve diabetic patients (9 patients with normoalbuminuria, 2 patients with microalbuminuria and 1 patient with macroalbuminuria) and 9 healthy controls were studied. Urinary cell pellet was obtained via centrifugation from fresh urine. The pellet was cytospun for immunofluorescence. Urinary podocytes were identified by colocalization of the podocyte specific markers nephrin and podocin, as well as synaptopodin and podocin. The podocytes-to-creatinine ratio was calculated for semiquantification of podocyturia. We found that urinary podocytes were absent in the healthy controls, as expected. On the other hand, all diabetic patients, even those with normoalbuminuria, demonstrated presence of urinary podocytes. The mean podocyte-to-creatinine ratio in the diabetic patients with normoalbuminuria was 1222.5 podocytes/mg creatinine, as compared with 119.3 podocytes/mg creatinine in the microalbuminuria group. The degree of podocyturia did not correlate with the amount of albuminuria. In conclusion, we found significant podocyturia in normoalbuminuric diabetic patients, revealing podocyte injury in this presumed "unaffected" population. Thus, we believe that podocyturia is an earlier marker of DN than microalbuminuria, and that it may be a better predictor of progression, since once lost, podocytes do not regenerate. Given our small sample size, we will need to validate our results in larger group, and to follow these patients prospectively for renal outcomes.

Research paper thumbnail of Home Dialysis: A Majority Chooses It, a Minority Gets It

Blood Purification, 2021

Introduction: When choosing a modality for outpatient renal replacement therapy, patients and med... more Introduction: When choosing a modality for outpatient renal replacement therapy, patients and medical providers have 3 options to choose from in-center hemodialysis (HD), home HD (HHD), and peritoneal dialysis (PD). In 2017, just over 10% of incident ESKD patients were on a home dialysis modality. We set out to determine outcomes of dialysis modality education in both pre-dialysis and dialysis patients. Moreover, we examined barriers that preclude patients from choosing home dialysis. Methods: This was a single-center, retrospective study looking at patients who were referred to the CKD educator for dialysis modality education between January 1, 2019, and March 31, 2020. Patient demographics, preferred language of communication, stage of renal disease, and reasons for patients’ refusal to undertake a home dialysis modality were recorded. Patients’ average household income and driving distance to our home dialysis unit were calculated using their home zip code. Results: 167 patients ...

Research paper thumbnail of Telenephrology with Remote Peritoneal Dialysis Monitoring during Coronavirus Disease 19

American Journal of Nephrology, 2020

Research paper thumbnail of Acute Start Peritoneal Dialysis during the COVID-19 Pandemic: Outcomes and Experiences

Journal of the American Society of Nephrology, 2020

Research paper thumbnail of Outcomes of Patients on Maintenance Dialysis Hospitalized with COVID-19

Clinical Journal of the American Society of Nephrology, 2020

Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-... more Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had devastating effects worldwide. Patients with kidney failure on dialysis may have a higher risk of worse outcomes. Reports from China found that these patients with SARS-CoV-2 had fewer symptoms and required less intensive care than expected (1). A recent observational study of hospitalized patients with kidney failure and COVID-19 reported 31% mortality (2). However, this study lacked a comparator group, and thus, it is unclear if this high mortality would be found in patients without kidney failure with a similarly high comorbidity burden. Therefore, we conducted this retrospective cohort study of patients with kidney failure hospitalized with COVID-19 in the Mount Sinai Health Care System (MSHS) and compared it with a propensity-matched cohort without kidney failure. Only patients age $18 years admitted between March 15 and June 7, 2020, with laboratoryconfirmed SARS-CoV-2 within 48 hours of admission were included. Patients with kidney failure were identified by a combination of kidney failure diagnosis and dialysis procedure International Classificaton of Diseases codes. Patients with previous kidney transplants were not excluded if they had kidney failure at the time of study. The Mount Sinai Institutional Review Board approved this research. We propensity matched patients with kidney failure to those without kidney failure (1:5) without use of a caliper by age, sex, race/ethnicity, comorbidities (atrial fibrillation, coronary artery disease, cancer, congestive heart failure, diabetes, hypertension, chronic obstructive pulmonary disease, asthma, peripheral vascular disease, stroke, and liver disease), body mass index (kilograms per meter 2), admission facility, and admission week using nearest neighbor matching. Despite propensity matching, significant differences in patient characteristics remained between kidney failure and non-kidney failure cohorts. Therefore, we performed logistic regression analysis after controlling for age, diabetes, hypertension, stroke, coronary artery disease, and congestive heart failure to determine the association between kidney failure and mechanical ventilation, intensive care unit (ICU) admission, and

Research paper thumbnail of COVID-19–Associated Acute Kidney Injury and Quantified Protein Catabolic Rate: A Likely Effect of Cytokine Storm on Muscle Protein Breakdown

Kidney Medicine, 2021

Previously we reported a cohort of patients with coronavirus disease 2019 (COVID-19)-associated a... more Previously we reported a cohort of patients with coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) with striking biochemical evidence of tissue breakdown in the absence of apparent rhabdomyolysis. We sought to quantify the extent of tissue catabolism in similar patients. Study Design: During acute peritoneal dialysis (PD) in patients with COVID-19-associated AKI, we measured urea Kt/V adequacy and calculated the daily urea nitrogen generation rate while quantifying daily protein intake.

Research paper thumbnail of Bilateral Renal Artery Thrombosis in a Patient With COVID-19

Kidney Medicine, 2020

Reports of the incidence of acute kidney injury in patients with coronavirus disease 2019 (COVID-... more Reports of the incidence of acute kidney injury in patients with coronavirus disease 2019 (COVID-19) have varied greatly from 0.5% to as high as 39%, with onset generally within 7 days from time of admission. The nature of the kidney insult is acute tubular necrosis, immune cell infiltration, or rhabdomyolysis, as demonstrated in autopsy reports. Moreover, infection with COVID-19 has been associated with coagulation abnormalities, as well as complement-mediated generalized thrombotic microvascular injury. These patients have been found to have high D-dimer, fibrin degradation product, and fibrinogen values, an elevated international normalized ratio, normal partial thromboplastin time, and normal platelet count values. Renal artery thrombosis is a rare condition, the most common cause of which is atrial fibrillation. However, bilateral completely occlusive renal artery thrombosis is even rarer. We present a case of a patient with COVID-19 on systemic anticoagulation therapy who presented with a serum creatinine level of 6.04 mg/dL requiring the initiation of kidney replacement therapy and was found to have bilateral renal artery thrombosis.

Research paper thumbnail of Home Dialysis Training for Fellows: Privilege or Necessity?

American Journal of Kidney Diseases, 2020

T here is a great discrepancy between the modality that nephrologists would choose if they themse... more T here is a great discrepancy between the modality that nephrologists would choose if they themselves were to start dialysis and the reality of the current dialysis situation in the United States. In a 2010 survey reported by Merighi et al, 1 629 practicing US nephrologists were asked "If your kidneys failed and there was a 5-year wait for a transplant, which type of dialysis would you choose?" Only 6% chose in-center hemodialysis (HD); by contrast, of the prevalent dialysis population in that same year, 92% were receiving incenter HD. One would be pressed to find another situation for which there is such a stark difference between physicians' and patients' choices. This suggests that nephrologists are aware of benefits associated with home dialysis and would choose home dialysis for themselves, but other factors, both medical and nonmedical, have an important role in determining the dialysis modality that patients receive. Patient factors include comorbid conditions, psychosocial and financial barriers, and patient and partner education about home dialysis. 2 Provider factors, as noted in a recent NKF-KDOQI conference outcomes report, 2 include a lack of education and perceived competence in prescribing home dialysis. This should come as little surprise. Although the number of kidney replacement therapy (KRT) patients in the United States continues to grow, increasing from 304,420 in 1996 to 726,331 in 2016, 3 KRT modality choice continues to be lopsided, with 87.5% of incident patients with kidney failure in 2016 receiving HD, 9.7% receiving peritoneal dialysis (PD), and only 2.8% receiving a kidney transplant. 3 Of patients who initiated HD, only 2% started with home HD (HHD), whereas an overwhelming 98% started with in-center dialysis. Among prevalent dialysis patients, numbers are similar, with 87.6% receiving in-center HD; 1.8%, HHD; and 10.1%, PD. 3 This low prevalence leads to a lack of exposure to home therapies among US nephrologists, thereby reducing expertise and comfort in prescribing and caring for home dialysis patients. 4

Research paper thumbnail of Acute Kidney Injury In Hospitalized Patients Who Underwent Percutaneous Kidney Biopsy

Background Performing a kidney biopsy is necessary to accurately diagnose diseases such as glomer... more Background Performing a kidney biopsy is necessary to accurately diagnose diseases such as glomerulonephritis and tubulointerstitial nephritis, among other such conditions. These conditions predispose patients to chronic kidney disease, as well as acute kidney injury (AKI). Notably, most epidemiological studies describing AKI have not investigated this patient population. Methods Included patients admitted to the nephrology ward of a tertiary hospital who underwent percutaneous kidney biopsy. AKI was diagnosed based on the Kidney Disease: Improving Global Outcomes criteria. Results Of the 223 patients investigated, 140 (62.8%) showed AKI. Of these, 91 (65%), 19 (13.6%), and 30 (21.4%) presented with AKI classified as stages 1, 2, and 3, respectively. The primary indication for performing biopsy was nephrotic syndrome or nephrotic proteinuria (73 [52.1%] in the AKI vs. 51 [61.4%] in the non-AKI group, p=0.048). Focal segmental glomerulosclerosis was the most prevalent primary disease...

Research paper thumbnail of Retinoic acid improves nephrotoxic serum-induced glomerulonephritis through activation of podocyte retinoic acid receptor α

Kidney international, Dec 27, 2017

Proliferation of glomerular epithelial cells, including podocytes, is a key histologic feature of... more Proliferation of glomerular epithelial cells, including podocytes, is a key histologic feature of crescentic glomerulonephritis. We previously found that retinoic acid (RA) inhibits proliferation and induces differentiation of podocytes by activating RA receptor-α (RARα) in a murine model of HIV-associated nephropathy. Here, we examined whether RA would similarly protect podocytes against nephrotoxic serum-induced crescentic glomerulonephritis and whether this effect was mediated by podocyte RARα. RA treatment markedly improved renal function and reduced the number of crescentic lesions in nephritic wild-type mice, while this protection was largely lost in mice with podocyte-specific ablation of Rara (Pod-Rara knockout). At a cellular level, RA significantly restored the expression of podocyte differentiation markers in nephritic wild-type mice, but not in nephritic Pod-Rara knockout mice. Furthermore, RA suppressed the expression of cell injury, proliferation, and parietal epitheli...

Research paper thumbnail of Hypertension in Pregnancy

Cardiology in Review, 2010

ABSTRACT

Research paper thumbnail of Hemodialysis venous needle dislodgement to the heart: a case report

The Journal of Vascular Access, 2012

Research paper thumbnail of Hemodialysis venous needle dislodgement to the heart: a case report

The Journal of Vascular Access, 2012

Research paper thumbnail of A comparison of podocyturia, albuminuria and nephrinuria in predicting the development of preeclampsia: a prospective study

PloS one, 2014

Preeclampsia, a hypertensive multisystem disease that complicates 5-8% of all pregnancy, is a maj... more Preeclampsia, a hypertensive multisystem disease that complicates 5-8% of all pregnancy, is a major cause for maternal and fetal mortality and morbidity. The disease is associated with increased spontaneous and evoked preterm birth and remote cardio-renal disorders in the mother and offspring. Thus the ability to predict the disease should lead to earlier care and decreased morbidity. This has led to fervent attempts to identify early predictive biomarkers and research endeavors that have expanded as we learn more regarding possible causes of the disease. As preeclampsia is associated with specific renal pathology including podocyte injury, early urinary podocyte (podocyturia), or the podocyte specific proteinuria nephrin in the urine (nephrinuria), as well as the more easily measured urinary albumin (albuminuria), have all been suggested as predictive markers. We performed a prospective study recruiting 91 pregnant women (78 of whom were high risk) and studied the predictive abilit...

Research paper thumbnail of Expression of Notch pathway proteins correlates with albuminuria, glomerulosclerosis, and renal function

Kidney International, 2010

Recent studies indicate that the Notch signaling pathway plays an important role in the developme... more Recent studies indicate that the Notch signaling pathway plays an important role in the development of diabetic kidney disease and focal segmental glomerulosclerosis (FSGS). Here we analyzed the degree of expression and localization of Notch ligands (Jagged1 and Delta1) and activated (cleaved) receptors (Notch1 and Notch2) in healthy human kidneys and in renal biopsies from a wide variety of kidney diseases. These included patients with minimal change disease, membranous nephropathy, lupus nephritis ISN/RPS classes III/IV/V, hypertensive nephrosclerosis, crescentic glomerulonephritis, tubulointerstitial fibrosis, IgA nephropathy, diabetic kidney disease, and FSGS. We found that cleaved Notch1, Notch2, and Jagged1 are expressed on podocytes in proteinuric nephropathies and their level of expression correlated with the amount of proteinuria across all disease groups. The degree of glomerulosclerosis correlated with podocyte expression of cleaved Notch1, while the severity of tubulointerstitial fibrosis and the estimated glomerular filtration rate correlated with expression of cleaved Notch1 in the tubulointerstitium. Hence, our results raise the possibility that Notch pathway activation is a common mechanism in the pathophysiology of a wide range of acquired renal diseases.

Research paper thumbnail of The story of Notch and chronic kidney disease

Current Opinion in Nephrology and Hypertension, 2011

Purpose of the review-The Notch pathway is an evolutionary conserved cell-cell communication mech... more Purpose of the review-The Notch pathway is an evolutionary conserved cell-cell communication mechanism that plays a key role in kidney development. Here we will discuss a number of recently published papers describing the role of Notch signaling in kidney development, homeostasis, injury and repair. Recent findings-Recent gene expression studies identified regulation of the Notch pathway in patients with chronic kidney disease (CKD). Mechanistic experiments performed using transgenic and knockout mouse models indicate that Notch plays an important functional role in the development of proteinuria and renal fibrosis. Inhibition of the Notch pathway ameliorated diabetic kidney disease, nephrotic syndrome and fibrosis in different rodent models. Summary-An increasing amount of evidence suggests that Notch plays a role in CKD development. Understanding the role of Notch signaling in the kidney can aid in the development of new therapeutics for CKD.

Research paper thumbnail of 151: Intradialytic Use of Heparin: Is Heparin Necessary for Stable Chronic Hemodialysis Treatments?

American Journal of Kidney Diseases, 2010

Diuretics are thought to contribute to deterioration of renal function in patients with heart fai... more Diuretics are thought to contribute to deterioration of renal function in patients with heart failure (HF). Renal dysfunction and hyponatremia are both known to be associated with increased morbidity and mortality in these patients. Vasopressin receptor antagonists (VRA) and Adenosine-A1 receptor antagonists (A1RA) represent emerging pharmacological therapies that potentially lack the renal adverse effects of diuretics. This study explores the currently available data on the impact of these agents on kidney-related parameters. Articles cited in PubMed database from 1980 to 2009 using key words: "vasopressin receptor antagonist", "ADH-receptor antagonist", Adenosine-A1 receptor Antagonists", and "heart failure" were searched. Those clinical randomized controlled trials that exclusively included HF population were identified, and relevant articles were selected. The results of these studies were then reviewed and compared with regards to kidneyrelated parameters. A total of 27 and 22 relevant articles were identified for VRA and A1RA respectively. Nine randomized, placebo-controlled trials were selected to be included in this study for VRA, and 6 for A1RA. For VRA, 4 studies (44.5%) could not find any significant change in serum sodium levels, and the rest showed only a modest rise (e.g.≤4meq/l). Seven studies (77.8%) did not find any significant change in renal function. For A1RA, 3 studies (50%) did not show any significant change in renal function, and only two studies (33%) found increase in urine volume. While there is a promising theoretical basis and possible cardiac benefits for use of VRA and A1RA as adjunct therapy for patients with HF, currently available data show only modest beneficial impact on kidney-related parameters for both therapies. Future large-sized trials are clearly needed to further evaluate these effects and their potential impact on morbidity and mortality of patients with HF.

Research paper thumbnail of Urinary Albumin vs. Urinary Nephrin in Predicting the Development of Preeclampsia

American Journal of Kidney Diseases, 2012

Despite the high prevalence of preeclampsia, the ability to predict its occurrence is still probl... more Despite the high prevalence of preeclampsia, the ability to predict its occurrence is still problematic. There is evidence that alterations in the podocyte, a specialized visceral epithelial cell that lines the glomerular filtration barrier, may be linked to the pathogenesis of preeclampsia. We proposed to study whether markers of podocyte injury, in the form of urinary albumin and urinary nephrin, would be predictive of preeclampsia when measured early in pregnancy in obstetric patients who are at high risk of developing complications. We conducted a prospective study on 67 high risk obstetric patients (chronic hypertension, diabetes mellitus of any type, chronic kidney disease, SLE) and 14 healthy control obstetric patients in their 2 nd and 3 rd trimester of gestation. During the subjects' clinic visit, a 20 ml of urine sample was analyzed for random urine albumin and urine creatinine concentration using standard laboratory techniques. Urine nephrin concentration was measured using an enzyme-linked immunosorbent assay (Exocell Inc., Philadelphia, PA). Urine albumin-creatinine ratio (UACR) and urine nephrin-to-creatinine ratio (UNCR) were determined to control for the concentration of the urine. These subjects were followed until delivery. Unpaired parametric t-test analysis revealed that UACR in the 2 nd and 3 rd trimester were significantly higher for patients who developed preeclampsia as compared with those who didn't (p=0.04 and p=0.006 respectively). Similarly, UNCR in the 2 nd and 3 rd trimester also showed significantly higher levels (p=0.01 and p=0.004 respectively). When 2 nd and 3 rd trimester patients were combined, both UACR and UNCR continued to demonstrate significant differences between these two patients groups (p=0.01 and p=0.0005 respectively). We conclude that both UACR and UNCR are predictive of the development of preeclampsia when measured as early as the 2 nd trimester in pregnancy.

Research paper thumbnail of The Association between Prevalence of Peritoneal Dialysis versus Hemodialysis and Patients’ Distance to Dialysis-Providing Facilities

Kidney360, 2021

BackgroundAccessibility to dialysis facilities plays a central role when deciding on a patient’s ... more BackgroundAccessibility to dialysis facilities plays a central role when deciding on a patient’s long-term dialysis modality. Studies investigating the effect of distance to nearest dialysis-providing unit on modality choice have yielded conflicting results. We set out to investigate the association between patients’ dialysis modality and both the driving and straight-line distances to the closest HD- and PD-providing units.MethodsAll patients with ESKD who initiated in-center HD and PD in 2017, were 18–90 years old, and were on dialysis for ≥30 days were included. Patients in residence zip codes in nonconterminous United States or lived >90 miles from the nearest HD-providing unit were excluded.ResultsA total of 102,247 patients in the United States initiated in-center HD and PD in 2017. Compared with patients on HD, patients on PD had longer driving distances to their nearest PD unit (4.4 versus 3.4 miles; P<0.001). Patients who lived >30 miles from the nearest HD unit we...

Research paper thumbnail of The Association between Prevalence of Peritoneal Dialysis versus Hemodialysis and Patients’ Distance to Dialysis-Providing Facilities

Kidney360, 2021

BackgroundAccessibility to dialysis facilities plays a central role when deciding on a patient’s ... more BackgroundAccessibility to dialysis facilities plays a central role when deciding on a patient’s long-term dialysis modality. Studies investigating the effect of distance to nearest dialysis-providing unit on modality choice have yielded conflicting results. We set out to investigate the association between patients’ dialysis modality and both the driving and straight-line distances to the closest HD- and PD-providing units.MethodsAll patients with ESKD who initiated in-center HD and PD in 2017, were 18–90 years old, and were on dialysis for ≥30 days were included. Patients in residence zip codes in nonconterminous United States or lived >90 miles from the nearest HD-providing unit were excluded.ResultsA total of 102,247 patients in the United States initiated in-center HD and PD in 2017. Compared with patients on HD, patients on PD had longer driving distances to their nearest PD unit (4.4 versus 3.4 miles; P<0.001). Patients who lived >30 miles from the nearest HD unit we...

Research paper thumbnail of 281: Urinary Excretion of Podocytes as an Early Marker of Diabetic Nephropathy

American Journal of Kidney Diseases, 2010

Pathogenesis of diabetic nephropathy (DN) is related to podocyte injury and loss. Podocytes, whic... more Pathogenesis of diabetic nephropathy (DN) is related to podocyte injury and loss. Podocytes, which are located on the outer surface of the glomerular basement membrane, appear in the urine as a result of detachment. Microalbuminuria has been traditionally used to detect the onset of DN; its appearance usually prompts aggressive treatment. The aim of this study is to determine whether the podocytes are lost in diabetic patients even before the appearance of microalbuminuria, and that it may serve as an earlier marker of DN. Twelve diabetic patients (9 patients with normoalbuminuria, 2 patients with microalbuminuria and 1 patient with macroalbuminuria) and 9 healthy controls were studied. Urinary cell pellet was obtained via centrifugation from fresh urine. The pellet was cytospun for immunofluorescence. Urinary podocytes were identified by colocalization of the podocyte specific markers nephrin and podocin, as well as synaptopodin and podocin. The podocytes-to-creatinine ratio was calculated for semiquantification of podocyturia. We found that urinary podocytes were absent in the healthy controls, as expected. On the other hand, all diabetic patients, even those with normoalbuminuria, demonstrated presence of urinary podocytes. The mean podocyte-to-creatinine ratio in the diabetic patients with normoalbuminuria was 1222.5 podocytes/mg creatinine, as compared with 119.3 podocytes/mg creatinine in the microalbuminuria group. The degree of podocyturia did not correlate with the amount of albuminuria. In conclusion, we found significant podocyturia in normoalbuminuric diabetic patients, revealing podocyte injury in this presumed "unaffected" population. Thus, we believe that podocyturia is an earlier marker of DN than microalbuminuria, and that it may be a better predictor of progression, since once lost, podocytes do not regenerate. Given our small sample size, we will need to validate our results in larger group, and to follow these patients prospectively for renal outcomes.