ACTH treatment for management of nephrotic syndrome: A systematic review and reappraisal.
DESCRIPTIVE statistics; TREATMENT effectiveness; MEDICAL information storage & retrieval systems; MEDLINE; SYSTEMATIC reviews (Medical research); NEPHROTIC syndrome treatment; ADRENOCORTICOTROPIC hormone; INFORMATION storage & retrieval systems – Medical care
BACKGROUND: In recent years, the use of adrenocorticotropic hormone (ACTH) therapy for treatment of proteinuria due to nephrotic syndrome (NS) has been heavily explored. ACTH therapy, which comes in the natural (H. P. Acthar Gel) or synthetic (tetracosactide) form, has resulted in remission in patients with immunosuppressive and steroid-resistant NS. However, the exact efficacy of ACTH therapy in the NS etiologies, such as membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), lupus nephritis (LN), IgA nephropathy (IgAN), and membranoproliferative glomerulonephritis (MPGN), has not been determined. OBJECTIVE: This systematic review analyzed the published literature on ACTH therapy in various NS etiologies to determine its efficacy. METHODS: A comprehensive search of MEDLINE, EMBASE, and Cochrane databases was conducted for articles through June 2019. An additional search was performed on clinicaltrials.gov to search for additional trials and cross reference the results of our database search. The literature which studied synthetic or natural ACTH treatment in patients with known etiologies of NS was included. Studies were excluded when they consisted of a single case report or did not analyze the lone effect of ACTH in NS. RESULTS: The initial search yielded a total of 411 papers, and 22 papers were included. In 214 MN patients, there was an overall remission of 40% (85/214) and an overall remission of 43% (42/98) in FSGS patients. In other etiologies, there were overall remissions of 78% (11/14), 31% (5/16), 40% (16/40), and 62% (8/13) in MCD, LN, IgAN, and MPGN patients, respectively. CONCLUSION: ACTH showed benefits in proteinuria reduction across all etiologies of NS. However, more randomized controlled studies with larger population sets and longer follow-ups are imperative to establish causal benefits. New studies into its efficacy in children are also necessary.
Chakraborty R; Mehta A; Nair N; Nemer L; Jain R; Joshi H; Raina R
International Journal of Nephrology
2020
2020-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1155/2020/2597079" target="_blank" rel="noreferrer noopener">10.1155/2020/2597079</a>
Acute kidney injury associated with urinary stone disease in children and young adults presenting to a pediatric emergency department.
AKI; kidney stones; pediatric; urinary stone disease (USD); urolithiasis
Background: Acute kidney injury (AKI) due to urinary stone disease (USD) is rare in adults; AKI rates in children with USD may be higher, and emerging data links stones to chronic kidney disease (CKD) development in adults. Methods: This study is a retrospective analysis of USD patients at a single pediatric hospital system's emergency department (ED). Patients were initially identified by USD ICD codes; USD was then confirmed by imaging or physician documentation; patients had to have baseline creatinine (Cr) and Cr in the ED for comparison to be included. AKI was defined by Kidney Disease: Improving Global Outcomes (KDIGO), Acute Kidney Injury Network (AKIN), and Pediatric Risk, Injury, Failure, Loss, End Stage (pRIFLE). Results: Of the 589 total visits, 264/589 (45%) had data to evaluate for AKI, 23% were AKI(+) and 77% were AKI(-). pRIFLE was most common (82%) and 18% were only positive by AKIN/KDIGO. AKI(+) were more likely to be younger (16.7 vs. 17.4 years, p = 0.046) and more likely to present with vomiting {odds ratio [OR] [95% confidence interval (CI)]: 2.4 [1.4-4.3], p = 0.002}; also, the proportion of AKI(+) was significantly higher in <18 vs. ≥18 years [26.9 vs. 15.5%, p = 0.032, OR (95% CI): 2.0 (1.1-3.9)]. Urinary tract infection (UTI) and obstruction rates were similar between groups. AKI(+) patients had a significant OR <1 suggesting less risk of receiving non-steroidal anti-inflammatory drugs (NSAIDs); however, 51% of them did receive NSAIDs during their ED encounter. AKI(+) patients were more likely to require admission to the hospital (53 vs. 32%, p = 0.001). Conclusion: We have demonstrated a novel association between USD-induced renal colic and AKI in a group of young adults and children. AKI(+) patients were younger and were more likely to present with vomiting. AKI(+) patients did not have higher rates of obstruction or UTI, and 51% of AKI(+) received NSAIDs.
Farris N; Raina R; Tibrewal A; Brown M; Colvis M; Schwaderer A; Kusumi K
Frontiers in Pediatrics
2020
1905-07
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journalArticle
<a href="http://doi.org/10.3389/fped.2020.591520" target="_blank" rel="noreferrer noopener">10.3389/fped.2020.591520</a>
An overview of rickets in children
prevention; vitamin D; mutations; animal-model; phosphate; chronic kidney disease; phosphorus; d-receptor; d-resistant rickets; hereditary hypophosphatemic rickets; hypocalcemia; hypophosphatemia; targeted ablation; vitamin-d-deficiency; x-linked hypophosphatemia
Rickets is a common bone disease worldwide that is associated with disturbances in calcium and phos- phate homeostasis and can lead to short stature and joint deformities. Rickets can be diagnosed based on history and physical examination, radiological features, and biochemical tests. It can be classified into 2 major groups based on phosphate or calcium levels: phosphopenic and calcipenic. Knowledge of cate- gorization of the type of rickets is essential for prompt diagnosis and proper management. Nutritional rickets is a preventable disease through adequate intake of vitamin D through both dietary and sunlight exposure. There are other subtypes of rickets, such as vitamin D-dependent type 1 rickets and vitamin D- dependent type 2 rickets (due to defects in vitamin D metabolism), renal rickets (due to poor kidney function), and hypophosphatemic rickets (vitamin D-resistant rickets secondary to renal phosphate wasting wherein fibroblast growth factor -23 (FGF-23) often plays a major role), which requires closer monitoring and supplementation with activated vitamin D with or without phosphate supplements. An important development has been the introduction of burosumab, a human monoclonal antibody to FGF- 23, which is approved for the treatment of X -linked hypophosphatemia among children 1 year and older.
Chanchlani R; Nemer P; Sinha R; Nemer L; Krishnappa V; Sochett E; Safadi F; Raina R
Kidney International Reports
2020
2020-07
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journalArticle
<a href="http://doi.org/10.1016/j.ekir.2020.03.025" target="_blank" rel="noreferrer noopener">10.1016/j.ekir.2020.03.025</a>
Association of pulse pressure, pulse pressure index, and ambulatory arterial stiffness index with kidney function in a cross-sectional pediatric chronic kidney disease cohort from the CKiD study.
inflammation; risk; children; blood-pressure; progression; ckd; AASI; chronic kidney disease; pulse pressure; pulse pressure index; aasi; albuminuria; dialysis patients; left-ventricular hypertrophy
The morbidity and mortality of adult and pediatric chronic kidney disease (CKD) and end-stage renal disease (ESRD) populations are mainly driven by cardiovascular disease (CVD). Improving CVD outcomes focuses on risk assessment of factors including diastolic blood pressure (DBP), systolic blood pressure (SBP), left ventricular mass index (LVMI), pulse pressure (PP), and pulse pressure index (PPi), which is calculated as PP/SBP. These markers are also proven predictors of CKD progression; however, their role in children has not been established. This study aims to evaluate the relationship between PP, PPi, ambulatory arterial stiffness index (AASI), and proteinuria with kidney function in pediatric CKD patients; it is a retrospective analysis of 620 patients (1-16 years) from the NIDDK Chronic Kidney Disease in Children (CKiD) registry. The authors analyzed data for three separate cohorts: an overall CKD as well as immunological versus non-immunological cause for CKD groups. An inverse relationship was found between SBP, DBP, and PP with iGFR and LVMI in the overall CKD group. Our immunological CKD subgroup showed significantly higher serum creatinine, SBP, DBP, and PP values with significantly lower serum albumin levels compared to the non-immunological group. There were no significant differences with iohexol-based glomerular filtration rate (iGFR), LVMI, PPi, or high-sensitivity C-reactive protein (hs-CRP) between the two groups. A subgroup analysis demonstrated that SBP, DBP, and PP all correlated significantly with LVMI in the immunological CKD patients but not the non-immunological subgroup. Additionally, AASI data in the overall CKD population were significantly correlated with PP, PPi, and DBP. This study is one of the first to correlate noninvasive measurements of vascular compliance including PP, PPi, and AASI with iGFR and LVMI in a pediatric CKD cohort. Improving our understanding of surrogate markers for early CVD is integral to improving the care of pediatric CKD population as these patients have yet to develop the hard end points of ESRD, heart failure, myocardial infarction, or stroke.
Raina R; Polaconda S; Nair N; Chakraborty R; Sethi S; Krishnappa V; Kapur G; Mhanna M; Kusumi K
Journal of Clinical Hypertension
2020
2020-06
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journalArticle
<a href="http://doi.org/10.1111/jch.13905" target="_blank" rel="noreferrer noopener">10.1111/jch.13905</a>
Challenges of long-term vascular access in pediatric hemodialysis: Recommendations for practitioners.
Pediatrics; hemodialysis; vascular access; central venous catheter; arteriovenous grafts
Kidney transplantation is the preferred treatment of end-stage renal disease in children. However, time to transplant varies, making a well-functioning long-term vascular access essential for performing hemodialysis efficiently and without disruption until a kidney becomes available. However, establishing long-term vascular access in pediatric patients can present distinct challenges due to this population's unique characteristics, such as smaller body size and lower-diameter blood vessels. There are three main pediatric long-term vascular access options, which include central venous catheters (CVC), arteriovenous fistula (AVF), and arteriovenous graft (AVG). CVC are currently the most widely used modality, although various studies and guidelines recommend AVF or AVG as the preferred option. Although AVF should be used whenever possible, it is crucial that clinicians consider factors such as patient size, physical exam findings, comorbidities, predicted duration of treatment to decide on the most optimal long-term vascular access modality. This article reviews the three long-term vascular access methods in children and the benefits and complications of each.
Raina R;Joshi H;Chakraborty R;Sethi SK
Hemodialysis International.
2020
2020-10-18
journalArticle
<a href="http://doi.org/10.1111/hdi.12868" target="_blank" rel="noreferrer noopener">10.1111/hdi.12868</a>
Changing the terminology from kidney replacement therapy to kidney support therapy.
dialysis; acute kidney injury; extracorporeal organ support; kidney replacement therapy; kidney support therapy
Kidney replacement therapy(KRT) is a common supportive treatment for renal dysfunction, especially acute kidney injury. However, critically ill or immunosuppressed patients with renal dysfunction often have dysfunction in other organs as well. To improve patient outcomes, clinicians began to initiate kidney replacement therapy in situations where non-renal conditions may lead to AKI, such as septic shock, hematopoietic stem cell transplantation, veno-occlusive renal disease, cardiopulmonary bypass, chemotherapy, tumor lysis syndrome, hyperammonemia, and various others. In this review, we discuss the use of various modes of kidney replacement therapy in treating renal and non-renal complications to illustrate why kidney support therapy is a more appropriate terminology than renal replacement therapy. This article is protected by copyright. All rights reserved. (This article is protected by copyright. All rights reserved.)
Raina R;Joshi H;Chakraborty R
Therapeutic Apheresis And Dialysis
2020
2020-09-18
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1111/1744-9987.13584" target="_blank" rel="noreferrer noopener">10.1111/1744-9987.13584</a>
Development of acute kidney injury following pediatric cardiac surgery.
Pediatrics; Acute kidney injury; Nephrology; Thoracic surgery
Acute kidney injury (AKI) in the pediatric population is a relatively common phenomenon. Specifically, AKI has been found in increasing numbers within the pediatric population following cardiac surgery, with up to 43% of pediatric patients developing AKI post-cardiac surgery. However, recent advances have allowed for the identification of risk factors. These can be divided into preoperative, intraoperative, and postoperative factors. Although the majority of pediatric patients developing AKI after cardiac surgery completely recover, this condition is associated with worse outcomes. These include fluid overload and increased mortality and result in longer hospital and intensive care unit stays. Detecting the presence of AKI has advanced; use of relatively novel biomarkers, including neutrophil gelatinase associated lipocalin, has shown promise in detecting more subtle changes in kidney function when compared to conventional methods. While a single, superior treatment has not been elucidated yet, novel functions of medications, including fenoldopam, theophylline and aminophylline, have been shown to have better outcomes for these patients. With the recent advances in identification of risk factors, outcomes, diagnosis, and management, the medical community can further explain the complexities of AKI in the pediatric population post-cardiac surgery.
Sharma A; Chakraborty R; Sharma K; Sethi SK; Raina R
Kidney Research and Clinical Practice
2020
2020-08-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.23876/j.krcp.20.053" target="_blank" rel="noreferrer noopener">10.23876/j.krcp.20.053</a>
Endothelin-1 as a therapeutic target in autosomal dominant polycystic kidney disease
proliferation; hypertension; receptor; expression; Urology & Nephrology; growth-factor; renal damage; endothelin-1; excretion; polycystic kidney disease; chronic kidney disease; ADPKD; endothelin-1 antagonists; autosomal dominant; tolvaptan; urinary endothelin-1; water permeability
Aims: Endothelin-1 (ET-1) is associated with the pathophysiology of autosomal dominant polycystic kidney disease (ADPKD) via cyst progression. Elevated concentrations of ET-1 in ADPKD correlate with many phenotypic changes in the kidney such as renal cyst development, interstitial fibrosis, and glomerulosclerosis. In addition, an imbalance between renal ETA and ETB receptors possibly leads to more severe disease progression. The objective of this review is to determine whether evaluating the efficacy of these drugs in treatment of cystic kidney disease may be a worthwhile aim, as determined by results from animal and human models. Materials and methods: PubMed/Medline, Embase, and Google Scholar databases were searched using the key words "endothelin, endothelin-1 antagonists, and autosomal dominant polycystic kidney disease". All animal and human studies describing the effects of endothelin and endothelin-1 antagonists in ADPKD subjects were included in the review. Results: Urinary ET-1 concentrations could serve as a noninvasive surrogate biomarker for kidney ET-1 levels, as it is inversely associated with eGFR, independent of age, sex, and blood pressure. Elevated urinary excretion of ET-1 may be a biomarker for early renal injury. Antagonization of ET-1 may hopefully be a novel therapy for slowing progression of kidney damage in ADPKD. Conclusion: Based on the literature reviewed in this manuscript, it is proposed that further research evaluating the efficacy of endothelin antagonists in treatment of cystic kidney disease is warranted. More human studies need to be performed with larger sample sizes. Therefore, the recommendation for treatment is inconclusive at this time.
Raina R; Chauvin A; Vajapey R; Khare A; Krishnappa V
Clinical Nephrology
2019
2019-06
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<a href="http://doi.org/10.5414/cn109598" target="_blank" rel="noreferrer noopener">10.5414/cn109598</a>
Hypertensive crisis in pediatric patients: An overview.
management; acute severe hypertension; hypertensive crisis; hypertensive emergency; hypertensive urgency
Hypertensive crisis can be a source of morbidity and mortality in the pediatric population. While the epidemiology has been difficult to pinpoint, it is well-known that secondary causes of pediatric hypertension contribute to a greater incidence of hypertensive crisis in pediatrics. Hypertensive crisis may manifest with non-specific symptoms as well as distinct and acute symptoms in the presence of end-organ damage. Hypertensive emergency, the form of hypertensive crisis with end-organ damage, may present with more severe symptoms and lead to permanent organ damage. Thus, it is crucial to evaluate any pediatric patient suspected of hypertensive emergency with a thorough workup while acutely treating the elevated blood pressure in a gradual manner. Management of hypertensive crisis is chosen based on the presence of end-organ damage and can range from fast-acting intravenous medication to oral medication for less severe cases. Treatment of such demands a careful balance between decreasing blood pressure in a gradual manner while preventing damage end-organ damage. In special situations, protocols have been established for treatment of hypertensive crisis, such as in the presence of endocrinologic neoplasms, monogenic causes of hypertension, renal diseases, and cardiac disease. With the advent of telehealth, clinicians are further able to extend their reach of care to emergency settings and aid emergency medical service (EMS) providers in real time. In addition, further updates on the evolving topic of hypertension in the pediatric population and novel drug development continues to improve outcomes and efficiency in diagnosis and management of hypertension and consequent hypertensive crisis.
Raina R;Mahajan Z;Sharma A;Chakraborty R;Mahajan S;Sethi SK;Kapur G;Kaelber D
Frontiers in Pediatrics
2020
1905-07
journalArticle
<a href="http://doi.org/10.3389/fped.2020.588911" target="_blank" rel="noreferrer noopener">10.3389/fped.2020.588911</a>
Impact of trauma center designation in pediatric renal trauma: national trauma data bank analysis.
Outcomes; National Trauma Data Bank; Renal trauma; Trauma level
INTRODUCTION: The pediatric kidney is the most common urinary tract organ injured in blunt abdominal trauma. Trauma care in the United States has been established into a hierarchical system verified by the American College of Surgeons (ACS). Literature evaluating management of pediatric renal trauma across trauma tier designations is scarce. OBJECTIVE: To examine the differences in the management and outcomes of renal trauma in the pediatric population based on trauma level designation across the United States. STUDY DESIGN: We performed a review of the ACS - National Trauma Data Bank database. Pediatric patients (age 0-18 years) who were treated for renal injury between years 2011-2016 were identified. Our primary outcome was the difference in any complication rate amongst Level I versus Non-Level I trauma centers. Management strategies were evaluated as secondary outcomes. Propensity score matching (PSM) was utilized to adjust for baseline differences between cohorts. Multivariable regression analysis was performed to determine the independent effects of individual factors on complications, operative intervention, minimally invasive procedure, and blood transfusions. RESULTS: Overall, 12,097 pediatric patients were diagnosed with renal trauma between 2011 and 2016 using target ICD-9 and AAST codes. After PSM, there was a total of 1623 subjects withing each group. No difference was identified between groups for occurrence on any complication [105 (6.5%) vs 114 (7.0%), p = 0.576. There were no differences in the rate of minimally invasive interventions [67 (4.1%) vs 48 (3.0%), p = 0.087], operative intervention [58 (3.6%) vs 68 (4.2%), p = 0.413], or nephrectomy [42 (2.6%) vs 47 (2.9%), p = 0.667] between Level I and Non-Level I trauma designations, respectively. Length of stay was longer in the Level I cohort compared to Non-Level I (days (SD)) [6.9 (8.8) vs 6.2 (7.9), p = 0.024. When specifically looking at risk factors associated with operative intervention, higher renal injury grade and injury severity score were highly correlated, whereas, trauma level designation was not found to be predictive for more aggressive management. DISCUSSION & CONCLUSION: Our results corroborate with previous literature that renal injury grade and injury severity score are strong predictors of morbidity, invasive management, and complications. Pediatric renal trauma was managed similarly across trauma center designations, with the rate of complication and intervention more prevalent in patients with high grade renal injuries and concomitant injuries. Further studies are necessary to identify patients who will benefit most from transfer to a level I center.
Mahran A; Fernstrum A; Swindle M; Mishra K; Bukavina L; Raina R; Narayanamurthy V; Ross J; Woo L
Journal of Pediatric Urology
2020
2020-07-24
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journalArticle
<a href="http://doi.org/10.1016/j.jpurol.2020.07.019" target="_blank" rel="noreferrer noopener">10.1016/j.jpurol.2020.07.019</a>
Reconstructive urology. Preoperative testing for urethroplasty is not associated with outcomes-a NQSIP study
low-risk; physicians
OBJECTIVE To assess the current practice of routine preoperative testing before urethroplasty and to determine if the results are clinically significant. METHODS Data was obtained from the National Surgical Quality Improvement Program (NSQIP) database. We identified 1527 patients who underwent urethroplasty from 2010 to 2017. Chi-square and one-way ANOVA tests were used to compare categorical and continuous variables, respectively. Multivariable logistic regression analyses were utilized to assess the rate of complications between testing groups. RESULTS A total of 8455 individual laboratory tests were performed on 1156 patients (average of 7 tests per patient), with only 959 labs (11.3%) showing abnormal results. Of the 1156 patients, 629 (54.4%) patients had at least one abnormal lab. Patients who had at least one abnormal preoperative lab were found to be significantly older (51.49 +/- 16.57 years vs 48.14 +/- 16.32 years; P < .001), and to be smokers (112 [17.8%] vs 63 [12%]; P = 0.005). Additionally, they were more likely to have diabetes mellitus (112 [17.8%] vs 63 [12%]; P < 0.001), dyspnea (18 [2.9%] vs 16 [3.0%]; P = .029), and ASA class >= 3 when compared to the group with normal preoperative labs. On a multivariable logistic regression, abnormal preoperative tests were not predictive of intra- or postoperative complications in patients with ASA <= 2 (n = 1112) when adjusted for age and race. In patients with ASA class >= 3, the only lab predictive of postoperative complications was an abnormal coagulation profile. CONCLUSION Obtaining routine preoperative labs, especially in patients with ASA <= 2, does not affect postoperative outcomes in patients undergoing urethroplasty. (c) 2020 Elsevier Inc.
Mishra K; Avila A; Mahran A; Raina R; Sidagam V; Ponsky LE; Gonzalez CM; Bukavina L
Urology
2020
2020-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1016/j.urology.2020.02.018" target="_blank" rel="noreferrer noopener">10.1016/j.urology.2020.02.018</a>
Renal manifestations of tuberous sclerosis complex.
angiomyolipoma; autosomal polycystic kidney disease; renal cystic disease; tuberous sclerosis; Von Hippel–Lindau disease
Tuberous sclerosis complex (TSC) is a genetic condition caused by a mutation in either the TSC1 or TSC2 gene. Disruption of either of these genes leads to impaired production of hamartin or tuberin proteins, leading to the manifestation of skin lesions, tumors, and seizures. TSC can manifest in multiple organ systems with the cutaneous and renal systems being the most commonly affected. These manifestations can secondarily lead to the development of hypertension, chronic kidney disease, and neurocognitive declines. The renal pathologies most commonly seen in TSC are angiomyolipoma, renal cysts, and less commonly, oncocytomas. In this review, we highlight the current understanding on the renal manifestations of TSC along with current diagnosis and treatment guidelines. (Copyright: Nair N et al.)
Nair N;Chakraborty R;Mahajan Z;Sharma A;Sethi SK;Raina R
Journal Of Kidney Cancer And VHL
2020
2020-08-27
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.15586/jkcvhl.2020.131" target="_blank" rel="noreferrer noopener">10.15586/jkcvhl.2020.131</a>