Glomerulonephritis.

Glomerulonephritis (GN) encompasses several disorders that cause glomerular inflammation and injury through an interplay of immune-mediated mechanisms, host characteristics, and environmental triggers, such as infections. GN can manifest solely in the kidney or in the setting of a systemic illness, and presentation can range from chronic and relatively asymptomatic hematuria to fulminant renal failure. Classic acute GN is characterized by hematuria, edema, and hypertension, the latter 2 of which are the consequence of sodium and water retention in the setting of renal impairment. Although presenting signs and symptoms and a compatible clinical history can suggest GN, serologic and urinary testing can further refine the differential diagnosis, and renal biopsy can be used for definitive diagnosis. Treatment of GN can include supportive care, renin-angiotensin-aldosterone system blockade, immunomodulatory therapy, and renal transplant. Prognosis is largely dependent on the underlying cause of GN and can vary from a self-limited course to chronic kidney disease. This review focuses on lupus nephritis, IgA nephropathy, IgA vasculitis, and postinfectious GN.

Urology case report: Multifactorial bladder dysfunction in the setting of down syndrome.

A 16-year-old male patient with Down syndrome diagnosed with AKI and urinary tract infection was treated with meropenem for ESBL-positive E. coli in urine culture. Persistently elevated creatinine and persistent post-void residual (PVR) of >300 mL led to further testing, which revealed urethral stricture and a lower sacral Tarlov cyst. Due to no complete improvement with urethral dilatation, he underwent laminectomy and Tarlov cyst fenestration. Creatinine normalized, with increased urine output and robust flow. Due to a PVR of >100 mL, he received behavioral therapy, including sitting and timed voiding, and the PVR was reduced to <5 mL.

Time-dependent dual beneficial modulation of interferon-γ, interleukin 5, and Treg cytokines in asthma patient peripheral blood mononuclear cells by ganoderic acid B.

Th2 cytokines play a dominant role in the pathogenesis of allergic asthma. Interferon gamma (IFN-γ), a Th1 cytokine, links to therapeutic mechanisms of allergic asthma. Interleukin (IL)-10, a regulatory cytokine, is involved in the induction of immune tolerance. We previously demonstrated that Anti-Asthma Simplified Herbal Medicine Intervention (ASHMI) suppressed Th2 and increased IFN-γ in patients with asthma and in animal models, but its bioactive compound is unknown. Ganoderic acid beta (GAB) was isolated from Ganoderma lucidum (one herb in ASHMI). Human peripheral blood mononuclear cells (PBMCs) from adult patients with asthma were cultured with GAB or dexamethasone (Dex) in the presence of environmental allergens. The cytokine levels of IL-10, IFN-γ, IL-5, transcription factors T-bet, Foxp-3, and GATA3 were measured. Following 3-day culture, GAB, but not Dex, significantly increased IL-10 and IFN-γ levels by allergic patients' PBMCs. Following 6-day treatment, GAB inhibited IL-5 production, but IL-10 and IFN-γ remained high. Dex suppressed production of all three cytokines. GAB suppressed GATA3 and maintained Foxp-3 and T-bet gene expression, while Dex significantly suppressed GATA3 and T-bet expression. GAB simultaneously increased IL-10, IFN-γ associated with induction of T-bet and Foxp3, while suppressing IL-5, which was associated with suppression of GATA3, demonstrating unique beneficial cytokine modulatory effect, which distinguishes from Dex's overall suppression.

Nephrotic Syndrome.

Nephrotic syndrome (NS) encompasses a variety of disease processes leading to heavy proteinuria and edema. Minimal change disease (MCD) remains the most common primary cause of NS, as well as the most responsive to pharmacologic treatment with often minimal to no chronic kidney disease. Other causes of NS include focal segmental glomerulosclerosis, which follows MCD, and secondary causes, including extrarenal or systemic diseases, infections, and drugs. Although initial diagnosis relies on clinical findings as well as urine and blood chemistries, renal biopsy and genetic testing are important diagnostic tools, especially when considering non-MCD NS. Moreover, biomarkers in urine and serum have become important areas for research in this disease. NS progression and prognosis are variable and depend on etiology, with corticosteroids being the mainstay of treatment. Other alternative therapies found to be successful in inducing and maintaining remission include calcineurin inhibitors and rituximab. Disease course can range from recurrent disease relapse with or without acute kidney injury to end-stage renal disease in some cases. Given the complex pathogenesis of NS, which remains incompletely understood, complications are numerous and diverse and include infections, electrolyte abnormalities, acute kidney injury, and thrombosis. Pediatricians must be aware of the presentation, complications, and overall long-term implications of NS and its treatment.

Acute Kidney Injury Following Pediatric Liver Transplant.

OBJECTIVE: To determine the incidence, severity, and risk factors of postoperative acute kidney injury in pediatric liver transplant patients with and without inborn errors of metabolism. DESIGN: Retrospective cohort study. SETTING: Single-center PICU. PATIENTS: All children less than or equal to 18 years old who received a liver transplant between January 2009 and July 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Following exclusion criteria there were 92 transplant encounters. After excluding patients who received combined kidney-liver transplantation, acute kidney injury occurred in 57% of patients (N = 49), with 25.6% (N = 22) stage 1, 15.1% (N = 13) stage 2, and 16.3% (N = 14) stage 3. In an adjusted analysis, metabolic indication for transplant was not significantly associated with presence of acute kidney injury (p = 0.45). For the subset of patients without inborn errors of metabolism, the odds of having acute kidney injury was 1.50 (95% CI: 1.00-2.26) for each 1-unit increase in preoperative INR after adjusting for the covariates of age, preoperative albumin, CMV status of donor, and preoperative creatinine. In the full cohort, as well as the sample of children without inborn errors of metabolism, presence of acute kidney injury was associated with longer total hospital stay as well as number of ICU days. CONCLUSIONS: Acute kidney injury in the early postoperative period is common in pediatric liver transplant patients (57%), 31.4% of whom had severe disease. In patients without inborn errors of metabolism, each unit increase in preoperative INR suggests a higher risk of acute kidney injury after adjusting for covariates including preoperative creatinine. This finding suggests an association between the severity of preoperative synthetic liver function and the risk of developing postoperative acute kidney injury which requires further investigation.

Renal insufficiency in children born preterm: examining the role of neonatal acute kidney injury.

OBJECTIVE: To identify the prevalence of renal insufficiency (RI) in children with a history of prematurity and acute kidney injury (AKI). STUDY DESIGN: This prospective cohort study evaluated renal function in children born preterm at 5-9 years of age. Univariable analyses compared perinatal and follow-up data from subjects with and without AKI history, and with and without current RI. Regression analyses were attempted to model RI as a function of AKI and other clinical risk factors. RESULTS: Fifteen of 43 (35%) participants had previously undiagnosed RI. Only children with no AKI history or neonatal stage 1 AKI presented for follow-up. Children born preterm with a history of stage 1 AKI had higher serum creatinine (sCr) at follow-up, but were not more likely to have RI compared to children without stage 1 AKI history (RI prevalence 30% and 36% in AKI and non-AKI group, respectively). CONCLUSION: The high prevalence of RI in this preterm cohort at middle childhood follow-up highlights the need for routine kidney health assessments in this population. Large multicenter studies are needed to further characterize the impact of premature birth and mild AKI on renal function throughout childhood.

Rapid Biolayer Interferometry Measurements of Urinary CXCL9 to Detect Cellular Infiltrates Noninvasively After Kidney Transplantation.

INTRODUCTION: Measuring the chemokine CXCL9 in urine by enzyme-linked immunosorbent assay (ELISA) can diagnose acute cellular rejection (ACR) noninvasively after kidney transplantation, but the required 12- to 24-hour turnaround time is not ideal for rapid, clinical decision-making. METHODS: We developed a biolayer interferometry (BLI)-based assay to rapidly measure urinary CXCL9 in <1 hour. We validated this new assay versus standard ELISA in 86 urine samples from kidney transplantation recipients with various diagnoses. We then used BLI to analyze samples from 56 kidney transplantation recipients, including 46 subjects who experienced an acute rise in serum creatinine associated with biopsy-proven ACR (n = 22), subclinical rejection (n = 15), or no infiltrates (n = 9), and 10 stable kidney transplantation recipients with surveillance biopsies. To assess its usefulness in detecting adequacy of therapy we serially measured serum creatinine and urinary CXCL9 in 6 subjects after treatment for ACR, and correlated the results with histological diagnoses on follow-up biopsies. RESULTS: BLI accurately and reproducibly detected urinary CXCL9 in <1 hour. BLI-based results showed that urinary CXCL9 was >200 pg/ml in subjects with ACR and ≤100 pg/ml in subjects with stable kidney function without cellular infiltrates. In samples obtained after treatment for ACR, BLI CXCL9 measurements detected biopsy-proven intragraft infiltrates despite treatment-induced reduction in serum creatinine. DISCUSSION: Together, our proof-of-principle results demonstrate that BLI-based urinary CXCL9 detection has potential as a point-of-care noninvasive biomarker to diagnose and guide therapy for ACR in kidney transplantation recipients.

Nephrotic syndrome.

On the basis of observational studies, the most common cause of nephrotic syndrome in school-aged children is minimal change disease. On the basis of research evidence and consensus, corticosteroids are considered first-line therapy for treatment of nephrotic syndrome. On the basis of consensus, prednisone therapy should be initiated at doses of 60 mg/m2 per day (2 mg/kg per day) administered for 4 to 6 weeks, followed by 40 mg/m2 per dose (1.5 mg/kg) every other day for at least 6 to 8 weeks. On the basis of consensus and expert opinion, it is important to recognize and manage the complications that can arise in patients with nephrotic syndrome, such as dyslipidemia, infection, and thrombosis. On the basis of research evidence, consensus, and expert opinion, several alternative therapies have been observed to have variable efficacy in children with both corticosteroid-dependent and corticosteroid-resistant nephrotic syndrome, although caution must be exercised in the administration of these corticosteroid-sparing medications secondary to toxic adverse effects. On the basis of observational studies, the course of nephrotic syndrome in most patients is that of relapse and remission.

Immunosuppressive effects of erythropoietin on human alloreactive T cells.

Correction of anemia with erythropoietin (EPO) is associated with improved kidney transplant outcomes. Emerging evidence, predominantly from animal models, indicates that these observations may be erythropoiesis-independent and that EPO exhibits immunosuppressive properties. We examined the effects of EPO on human T-cell alloimmunity by first documenting that CD4(+) and CD8(+) T cells express EPO receptor (EPO-R) on their surfaces. In mixed lymphocyte reactions, EPO induced a dose-dependent decrease in allogeneic CD4(+) T-cell proliferation (EPO 1000 U/ml: 44.6%±22.9% of vehicle, P<0.05; 2000 U/ml: 11.1%±4% of vehicle, P<0.001) without inducing cell death. The effects required signals transmitted directly through the EPO-R expressed on T cells, resulting in diminished Th1 differentiation without effects on regulatory T-cell induction. Mechanistic studies revealed that EPO prevented IL-2-induced proliferation by uncoupling IL-2 receptor signaling, inhibiting phosphorylation of the intracellular intermediaries AKT and extracellular signal-regulated kinase that are known to mediate T-cell expansion. EPO treatment reduced expansion of human naïve CD4(+) T cells after adoptive transfer into NOD scid γc(null) mouse recipients, verifying the effects in vivo. Although activated T cells expressed CD131, an alternative EPO receptor, addition of a specific CD131 agonist peptide, ARA290, did not alter T-cell proliferation or cytokine production. Our findings link EPO-R signaling on T cells to inhibition of T-cell immunity, providing one mechanism that could explain the observed protective effects of EPO in kidney transplant recipients.