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Management of diabetes mellitus is a challenge for clinicians. Uncontrolled hyperglycemia increases the risk of microvascular and macrovascular complications, damaging the body systems. Although a number of antidiabetic drugs are available for therapeutic intervention, toxicity, loss of efficacy in chronic use and high cost of treatment have necessitated the search for new molecules to manage diabetes. Safety and cost are the main prerequisite for the new antidiabetic molecules. Medicinal plants and their purified phytochemicals have shown promising antidiabetic potential in the past few years. The flavonoids can be widely classified into different categories like anthocyanins, catechins, flavanols, flavones, flavanones etc. Some flavonoids have hypoglycemic properties. They may improve al-tered glucose and oxidative metabolisms of diabetic states. The hypoglycemic effect of some herbal extracts has been confirmed in human and animal models of type 2 diabetes mellitus (T2DM). Some of the important phytoconstituents from the classes of flavonoid have been discussed here. The current review summarizes the antidiabetic activity of flavonoids, the mechanism-based action of flavonoids that target the various metabolic pathways in humans. Keywords: Diabetes mellitus, Flavonoids, Medicinal plants, mechanisms of action, T2DM

Risk factors associated with the progression of acute kidney injury to chronic kidney disease in pediatric allogeneic hematopoietic cell transplantation (AlloHCT) recipients are not well described. We retrospectively investigated the risk factors for the progression to CKD in 275 AlloHCT recipients. AKI and CKD grading was defined according to the Kidney Disease Improving Global Outcomes classification. PRI90 was defined as persistent renal insufficiency (estimated GFR

While there are increasing reports of acute kidney injury among hospitalized adults with COVID-19, there is still limited information on renal complications associated with COVID-19 in children. The cause of kidney involvement in COVID-19 is likely multifactorial, and appears to involve a complex process, including complement dysregulation and thrombotic microangiopathy. We present a pediatric case of COVID-19 and renal failure due to thombotic microangiopathy, successfully treated with eculizumab.

Introduction Glomerular diseases are characterized by variable disease activity over many years. We aimed to analyze the relationship between clinical disease activity and duration of glomerular disease. Methods Disease activity in adults with chronic minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy (IgAN; first diagnostic biopsy >5 years before enrollment; Of Longstanding Disease [OLD] cohort, n = 256) followed at Columbia University Medical Center (CUMC), was compared with disease activity of an internal and external cohort of patients with first diagnostic biopsy, Graphical abstract

BACKGROUND Focal segmental glomerulosclerosis (FSGS) predisposes patients for risk of recurrent disease in allografts. METHODS We report a case of a recipient of an unrelated living donor renal transplant and discuss considerations for utilization of ofatumumab and eplerenone in treatment for recurrent FSGS. RESULTS The recipient was initially managed with scheduled plasmapheresis, intravenous immunoglobulin (IVIG), and rituximab post-transplant during index hospitalization. With notable recurrence of FSGS noted on kidney transplant biopsy, she was initially treated with additional plasmapheresis sessions leading to downtrend in proteinuria. The patient was then transitioned to LDL-A pheresis, which resulted again in uptrend in proteinuria. This prompted return to scheduled plasmapheresis sessions weekly, leading again to a downtrend in proteinuria. Albumin levels remained within normal range throughout her course. Following initiation of eplerenone and ofatumumab, the patient demonstrated normalization of urine protein:creatinine ratio and remission of FSGS recurrence without need for additional apheresis. CONCLUSIONS With notable risk of recurrence of FSGS in kidney transplants leading to allograft failure, the use of ofatumumab and eplerenone in conjunction should be considered for management to induce remission.

Introduction Recurrent focal and segmental glomerulosclerosis (FSGS) in kidney transplant recipients is associated with lower graft survival and increased morbidity. There are limited data to guide the decision to re-transplant patients with transplant failure due to FSGS recurrence. We aimed to evaluate outcomes in patients re-transplanted after having initial graft failure due to recurrent FSGS and to study physician attitudes and practice patterns. Methods Retrospective data from 10 centers were collected on 20 patients transplanted between January 1997 and September 2018. A survey was sent to nephrologist members of the Pediatric Nephrology Research Consortium. Results Mean patient age (years) was 9.8 ± 4.8 at first transplant and 15.9 ± 4.9 at re-transplantation. Pre-transplant plasmapheresis was used in 1 (5.3%) primary transplant vs. 7 (38.9%) re-transplants (p = .03). Nephrotic syndrome recurred in 14 patients (70%) after re-transplantation and was severe in 21.1% vs. 64.7% after first transplant (p = .04). Graft survival was significantly higher in the second transplant (p .009) with 70% having functioning grafts at a median of 25.2 months. Thirty-one physicians from 21 centers completed the survey, 94% indicated they would re-transplant such patients, 44.4% preferred a minimum waiting period before re-transplantation, 36.4% preferred living donors, and 22.2% indicated having protocols for re-transplantation at their centers. Conclusions Consideration for re-transplantation is high among pediatric nephrologists. Pre-transplant plasmapheresis was more frequent in re-transplanted patients. Nephrotic syndrome recurrence was less severe, with better graft survival. More data and a larger population are necessary to further evaluate outcome determinants and best practices in this special population.

Background Medullary sponge kidney (MSK) disease predisposes patients to recurrent nephrolithiasis, which affects one in every 5000 people in the United States. Methods We report a rare case of a pediatric recipient of a living donor MSK transplant and discuss considerations when discussing risks and benefits of accepting MSK allografts for this population. Results The recipient was admitted due to concerns for nephrolithiasis, hydronephrosis, and urinary tract infection at 1-month post-transplant. The hydronephrosis was resolved by surgical removal of an encrusted ureteral stent; this was followed by supplementation with oral medications to prevent future episodes of nephrolithiasis. The recipient did not have any further episodes after this as seen at a 1-year follow-up. The donor has remained well through this period. Conclusions With increasing organ shortages, the use of variety of donors may need to be considered to enlarge the organ pool.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a recently identified entity in association with COVID-19. AKI has been widely reported in patients with primary COVID-19 infection. However, there is a paucity of literature regarding renal injury in MIS-C. We aim to characterize AKI in MIS-C in this cohort identified at a major children's hospital in New York City during the COVID-19 pandemic. METHODS: We conducted a retrospective cohort study of children 0–20 years old admitted to Morgan Stanley Children's Hospital (MSCH) between April 18th and September 23rd, 2020. Patients were included if they met criteria for MIS-C on the basis of CDC guidelines. All patients were evaluated for the presence of AKI, and AKI was staged according to KDIGO criteria. RESULTS: Of the 57 children who met inclusion criteria, 46% (26 of 57) were found to have AKI. The majority of patients (58%; 15 of 26) were classified as KDIGO stage 1. AKI was present upon admission in 70% of those identified. All patients had resolution of AKI at discharge, with 61% achieving recovery by day 2. One patient required dialysis. When compared with those without renal injury, the AKI cohort was older (P

Risk factors associated with the progression of acute kidney injury to chronic kidney disease in pediatric allogeneic hematopoietic cell transplantation (AlloHCT) recipients are not well described. We retrospectively investigated the risk factors for the progression to CKD in 275 AlloHCT recipients. AKI and CKD grading was defined according to the Kidney Disease Improving Global Outcomes classification. PRI90 was defined as persistent renal insufficiency (estimated GFR 90 ml/min/1.73 m

In 2005, the Banff committee expanded the "borderline changes" category to include lesions with minimal (

Summary Chronic kidney disease (CKD) affects over 20 million individuals in the United States and 752 million individuals worldwide. 1 Progressive kidney disease that leads to the need for dialysis (end-stage renal disease or ESRD) or transplantation affects over 700,000 individuals in the United States. CKD is defined as abnormalities of kidney structure or function present for >3 months, with stratification based on estimated glomerular filtration rate category and the magnitude of albuminuria. 2 The Kidney Disease: Improving Global Outcomes group has updated the classification of CKD and changed the term “stage” to “grade,” as not all kidney disease is progressive, and noted that the presence or absence of albuminuria can greatly influence prognosis. 3 In this chapter, we describe in brief the primary nutritional and metabolic derangement in children and adults with CKD.

Risk factors associated with progression of AKI to CKD in pediatric AlloHCT recipients is not well described. We investigated the association between AKI and progression to CKD. A retrospective observational study of 275 patients post-AlloHCT age 1-21 years was performed with longitudinal follow up of three years. KDIGO staging for AKI and CKD universally applied by nephrologists to assess renal function was used. AKI defined as >0.3mg/dl increase from baseline creatinine. CKD defined as GFR 3months. GFR analyzed 90 days from the initial AKI episode was termed CKD90. Among patients that developed CKD90, CKD incidence and risk factors were analyzed 1 and 3 years post-AlloHCT. Univariate model for CKD risk factors included pre-transplant characteristics, infections, nephrotoxic agents and AKI parameters; risk factors with p Median age of 9.5±6 years, 99.6% patients had AKI. The median time to AKI was 34 days (92.8±206). Incidence of Grade 1, 2 and 3 AKI was 43%, 41% and 15%, respectively.GFR of 76.4% (210/274) met criteria for CKD (≥ stage 2) (Table 1). Majority of CKD90 patients were stage 2 CKD (35.7%) followed by stage 3 CKD (22.9%) (Table 1). Among the CKD90 patients who met criteria for CKD 1-year post AlloHCT, CKD stage 2 andCKD stage 3 were 37.1% and 16.9%, respectively (Figure 1). Upon multivariable analysis of risk factors for development of CKD at 1 and 3 year- CKD90, estimated baseline GFRand proteinuria were associated with progression to CKD (Table 2). Common factors associated with AKI in 1st 100 days of AlloHCT, such as bacterial and viral infections, tacrolimus levels >15ng/dl, vancomycin levels >20ng/dl, exposure to ganciclovir, foscarnet, cidofivir and ambisome were individually not associated with progression to CKD, indicating the possibility of multi-factorial contribution. Estimated baseline GFR, GFR at 90 days from the time of initial AKI episode and proteinuria can identify children at risk for CKD 1 year and 3 years post-AlloHCT.

Rationale & Objectives Glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A (IgA) nephropathy, share clinical presentations, yet result from multiple biological mechanisms. Challenges to identifying underlying mechanisms, biomarkers, and new therapies include the rarity of each diagnosis and slow progression, often requiring decades to measure the effectiveness of interventions to prevent end-stage kidney disease (ESKD) or death. Study Design Multicenter prospective cohort study. Setting & Participants Cure Glomerulonephropathy (CureGN) will enroll 2,400 children and adults with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (including IgA vasculitis) and a first diagnostic kidney biopsy within 5 years. Patients with ESKD and those with secondary causes of glomerular disease are excluded. Exposures Clinical data, including medical history, medications, family history, and patient-reported outcomes, are obtained, along with a digital archive of kidney biopsy images and blood and urine specimens at study visits aligned with clinical care 1 to 4 times per year. Outcomes Patients are followed up for changes in estimated glomerular filtration rate, disease activity, ESKD, and death and for nonrenal complications of disease and treatment, including infection, malignancy, cardiovascular, and thromboembolic events. Analytical Approach The study design supports multiple longitudinal analyses leveraging the diverse data domains of CureGN and its ancillary program. At 2,400 patients and an average of 2 years' initial follow-up, CureGN has 80% power to detect an HR of 1.4 to 1.9 for proteinuria remission and a mean difference of 2.1 to 3.0mL/min/1.73m2 in estimated glomerular filtration rate per year. Limitations Current follow-up can only detect large differences in ESKD and death outcomes. Conclusions Study infrastructure will support a broad range of scientific approaches to identify mechanistically distinct subgroups, identify accurate biomarkers of disease activity and progression, delineate disease-specific treatment targets, and inform future therapeutic trials. CureGN is expected to be among the largest prospective studies of children and adults with glomerular disease, with a broad goal to lessen disease burden and improve outcomes.

Introduction The Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients. Methods Patients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment. Results A total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years, P < 0.001), more frequently white (89.7% vs. 78.9%, P = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m2, P < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl, P < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%, P < 0.001). Conclusion This report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies.

There is scant literature describing the effect of glomerular disease on health-related quality of life (HRQOL). The Cure Glomerulonephropathy study (CureGN) is an international longitudinal cohort study of children and adults with four primary glomerular diseases (minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy). HRQOL is systematically assessed using items from the Patient-Reported Outcomes Measurement Informative System (PROMIS). We assessed the relationship between HRQOL and demographic and clinical variables in 478 children and 1115 adults at the time of enrollment into CureGN. Domains measured by PROMIS items included global assessments of health, mobility, anxiety, fatigue, and sleep impairment, as well as a derived composite measure incorporating all measured domains. Multivariable models were created that explained 7 to 32% of variance in HRQOL. Patient-reported edema consistently had the strongest and most robust association with each measured domain of HRQOL in multivariable analysis (adjusted β [95% CI] for composite PROMIS score in children, -5.2 [-7.1 to -3.4]; for composite PROMIS score in adults, -6.1 [-7.4 to -4.9]). Female sex, weight (particularly obesity), and estimated glomerular filtration rate were also associated with some, but not all, domains of HRQOL. Primary diagnosis, disease duration, and exposure to immunosuppression were not associated with HRQOL after adjustment. Sensitivity analyses and interaction testing demonstrated no significant association between disease duration or immunosuppression and any measured domain of HRQOL. Thus, patient-reported edema has a consistent negative association with HRQOL in patients with primary glomerular diseases, with substantially greater impact than other demographic and clinical variables.

Although there is less experience with its use in children than adults, apheresis can be a life-saving treatment modality in certain pediatric diseases. With attention to specific technical aspects of the treatment, especially circuit volume, apheresis can be safely performed in children of any age or size. Even in pediatric diseases where it is recognized as an important part of therapy, apheresis is unfortunately still underutilized in North America and there needs to be increased awareness of its role and its availability within the pediatric community. Apheresis has been used particularly in children with certain renal diseases, notably ANCA-associated nephritis, anti-GBM disease, and atypical HUS. In addition, it can improve outcomes in transplantation of children with FSGS and can be part of a pre-transplant strategy for children who are highly sensitized and at high risk for graft failure.

Over the last decade, therapy for lupus nephritis in children has begun to shift from the provision of long-term steroids and intravenous cyclophosphamide to regimens with limited or no cyclophosphamide, lower steroid burdens, and increased reliance on oral mycophenolate mofetil. As the molecular immunology underlying the pathophysiology of lupus is further discerned, more targeted therapies, including the use of monoclonal antibodies against immune cells or cell signaling factors, may come to play a larger role in the treatment of pediatric lupus. Similarly, as experience with autologous stem cell transplantation for therapy-resistant disease is gained in adults, its potential applicability to such situations in children may be clarified. Over the next few decades, children with lupus will benefit as well from the identification of new biomarkers that are both sensitive and specific to disease activity, allowing clinicians to more readily assess response to therapy and diagnose disease flare.

INTRODUCTION AND OBJECTIVES: Patients with obstructive uropathy and voiding dysfunction (OUeVD), such as posterior urethral valves, neurogenic bladder dysfunction and vesicoureteral reflux represent 20% to 30% of kidney transplantation (KT) population. Historically, these patients were denied KT due to suboptimal lower urinary tract (LUT) and frequent UTI that may compromise graft survival. A number of series reported acceptable KT outcomes in these patients compared to patients with normal LUT. We aim to evaluate the outcome of KT in pediatric patients with ESRD due to OUeVD compared to patients with ESRD due to medical renal disease (MRD) METHODS: A retrospective review of patients’ records who underwent KT at Cairo University Pediatrics Hospital from January 2007 through January 2014. Outcomes of KT done for ESRD due OUeVD (Group I) were evaluated and compared with outcomes for KT done for ESRD due to MRD (Group II). Multiple perioperative parameters were examined including ancillary procedures performed to optimize the UT for KT in addition to graft survival. RESULTS: 103 patients underwent KT in the reviewed period with 74/103 (71.8%) males and 29/103 (28.2%) females. Mean patient age at KT was 5.05 12.4 (2.2e18) years. Group I patients included 29 patients while Group II included 74 patients. All patients in Group I needed ancillary procedure prior to KT with 55.2% in Group II. Mean follow up was 3.34 1.63 (1e7) years and 2.12 1.08 (1e5) years for Group I and II, respectively. Mean creatinine at 12 months was 0.94 0.24mg/dL and 0.97 0.36mg/dL for Group I and II respectively, with no statistically significant difference between the 2 groups (p1⁄40.8). All Group I patients were maintaned on TMPeSMX antibiotic prophylaxis. There was no signifant difference in posteKT UTI rates (7/29 (24%) in Group I and 9/74 (12.3%) in Group II (p1⁄40.05). The incidence of backepressure was comparable in both groups, 6/29 (20.69%) in Group I and 16/74 (21.62%) in Group II (P value1⁄40.92). CONCLUSIONS: KT can be safely performed in pediatric patients with OUeVD with/without reconstructed LUT, with results comparable to patients with ESRD due to MRD. Antibiotic prophylaxis helps maintain acceptable UTI rates.

Although there is less experience with its use in children than adults, apheresis can be a life-saving treatment modality in certain pediatric diseases. With attention to specific technical aspects of the treatment, especially circuit volume, apheresis can be safely performed in children of any age or size. Even in pediatric diseases where it is recognized as an important part of therapy, apheresis is unfortunately still underutilized in North America and there needs to be increased awareness of its role and its availability within the pediatric community. Apheresis has been used particularly in children with certain renal diseases, notably ANCA-associated nephritis, anti-GBM disease, and atypical HUS. In addition, it can improve outcomes in transplantation of children with FSGS and can be part of a pre-transplant strategy for children who are highly sensitized and at high risk for graft failure.