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BackgroundWe report follow-up data from an ongoing prospective cohort study of COVID-19 in pediatric kidney transplantation through the Improving Renal Outcomes Collaborative (IROC).MethodsPatient-level data from the IROC registry were combined with testing, indication, and outcomes data collected to describe the epidemiology of COVID testing, treatment, and clinical outcomes; determine the incidence of a positive COVID-19 test; describe rates of COVID-19 testing; and assess for clinical predictors of a positive COVID-19 test.ResultsFrom September 2020 to February 2021, 21 centers that care for 2690 patients submitted data from 648 COVID-19 tests on 465 patients. Most patients required supportive care only and were treated as outpatients, 16% experienced inpatient care, and 5% experienced intensive care. Allograft complications were rare, with acute kidney injury most common (7%). There was 1 case of respiratory failure and 1 death attributed to COVID-19. Twelve centers that care for 1730 patients submitted complete testing data on 351 patients. The incidence of COVID-19 among patients at these centers was 4%, whereas the incidence among tested patients was 19%. Risk factors to predict a positive COVID-19 test included age > 12 years, symptoms consistent with COVID-19, and close contact with a confirmed case of COVID-19.ConclusionsDespite the increase in testing and positive tests over this study period, the incidence of allograft loss or death related to COVID-19 remained extremely low, with allograft loss or death each occurring in

There are limited data on the impact of COVID-19 in children with a kidney transplant (KT). We conducted a prospective cohort study through the Improving Renal Outcomes Collaborative (IROC) to collect clinical outcome data about COVID-19 in pediatric KT patients. Twenty-two IROC centers that care for 2732 patients submitted testing and outcomes data for 281 patients tested for SARS-CoV-2 by PCR. Testing indications included symptoms and/or potential exposures to COVID-19 (N = 134, 47.7%) and/or testing per hospital policy (N = 154, 54.8%). Overall, 24 (8.5%) patients tested positive, of which 15 (63%) were symptomatic. Of the COVID-19-positive patients, 16 were managed as outpatients, six received non-ICU inpatient care and two were admitted to the ICU. There were no episodes of respiratory failure, allograft loss, or death associated with COVID-19. To estimate incidence, subanalysis was performed for 13 centers that care for 1686 patients that submitted all negative and positive COVID-19 results. Of the 229 tested patients at these 13 centers, 10 (5 asymptomatic) patients tested positive, yielding an overall incidence of 0.6% and an incidence among tested patients of 4.4%. Pediatric KT patients in the United States had a low estimated incidence of COVID-19 disease and excellent short-term outcomes.

Pri-mary cilia sense environmental conditions, including osmolality, butwhether cilia participate in the osmotic response in renal epithelialcells is not known. The transient receptor potential (TRP) channelsTRPV4 and TRPM3 are osmoresponsive. TRPV4 localizes to cilia incertain cell types, while renal subcellular localization of TRPM3 is notknown. We hypothesized that primary cilia are required for maximalactivation of the osmotic response of renal epithelial cells and thatciliary TRPM3 and TRPV4 mediate that response. Ciliated [murineepithelial cells from the renal inner medullary collecting duct(mIMCD-3) and 176-5] and nonciliated (176-5Δ) renal cells ex-pressedTrpv4andTrpm3. Ciliary expression of TRPM3 was observedin mIMCD-3 and 176-5 cells and in wild-type mouse kidney tissue.TRPV4 was identified in cilia and apical membrane of mIMCD-3cells by electrophysiology and in the cell body by immunofluores-cence. Hyperosmolal stress at 500 mOsm/kg (via NaCl addition)induced the osmotic response genes betaine/GABA transporter (Bgt1)and aldose reductase (Akr1b3) in all ciliated cell lines. This inductionwas attenuated in nonciliated cells. A TRPV4 agonist abrogatedBgt1andAkr1b3induction in ciliated and nonciliated cells. A TRPM3agonist attenuatedBgt1andAkr1b3induction in ciliated cells only.TRPM3 knockout attenuatedAkr1b3induction. Viability under os-motic stress was greater in ciliated than nonciliated cells.Akr1b3induction was also less in nonciliated than ciliated cells when man-nitol was used to induce hyperosmolal stress. These findings suggestthat primary cilia are required for the maximal osmotic response inrenal epithelial cells and that TRPM3 is involved in this mechanism.TRPV4 appears to modulate the osmotic response independent ofcilia. [ABSTRACT FROM AUTHOR]

Background: Abnormal serum magnesium (Mg) concentrations are common and associated with worse mortality in kidney-transplant recipients. Many kidney and transplant-related factors affect Mg homeostasis. The concentration of the active form, ionized Mg (iMg), is not measured clinically, and total Mg (tMg) and iMg correlations have conflicted. We hypothesized that iMg and tMg concentrations show poor categorical agreement (i.e., low, normal, and high) in kidney-transplant recipients but that ionized calcium (iCa) correlates with iMg., Methods: We retrospectively evaluated hypomagnesemia in kidney-transplant recipients over a 2-yr period. We prospectively collected blood at 0-28 days post-transplant to measure correlations between iMg and iCa/tMg. iMg and iCa concentrations in the reference ranges of 0.44-0.65 and 1.0-1.3 mmol/L, respectively, were considered normal. Fisher's exact test and unweighted kappa statistics revealed category agreements. Pearson's correlation coefficients and linear regression measured correlations., Results: Among 58 retrospective kidney-transplant recipients, 54 (93%) had tMg<0.66 mmol/L, 28/58 (48%) received Mg supplementation, and 20/28 (71%) had tacrolimus dose adjustments during supplementation. In 13 prospective transplant recipients (N=43 samples), iMg and tMg showed strong category agreement ( P =0.0003) and correlation (r=0.71, P <0.001), whereas iMg and iCa did not ( P =0.7; r=-0.25, P =0.103, respectively)., Conclusions: tMg and iMg exhibited strong correlation following kidney transplantation. However, iCa may not be an accurate surrogate for iMg. Determining the effect of Mg supplementation and the Mg concentration where supplementation is clinically necessary are important next steps.

Background and Objectives: Kidney biopsy is an essential tool for the diagnosis and treatment of patients with kidney disease; however, because of its invasive nature, bleeding complications may arise., Design, Setting, Participants, & Measurements: We performed a meta-analysis of prospective or retrospective observational studies and randomized, controlled trials in pediatric patients undergoing native or transplant kidney biopsy in an inpatient or outpatient setting in MEDLINE-indexed studies from January 1998 to November 1, 2017 to determine the proportion of patients who develop hematoma, need blood transfusion, or need an additional intervention due to a complication after kidney biopsy., Results: Twenty-three studies of 5504 biopsies met inclusion criteria. The proportion of patients developing hematoma after biopsy was between 11% (95% confidence interval, 7% to 17%) and 18% (95% confidence interval, 9% to 35%) using two analyses that included different time periods. The proportion needing blood transfusion was 0.9% (95% confidence interval, 0.5% to 1.4%). The proportion needing an additional intervention due to postbiopsy complication was 0.7% (95% confidence interval, 0.4% to 1.1%). Secondary analysis was not possible due to lack of data in the original manuscripts on laboratory values, needle gauges, number of needle passes, age of patient, or performer (attending versus trainee). Analysis with metaregression found that use of real-time ultrasound during biopsy did not modify the risk for hematoma, requirement of a blood products transfusion, or requirement of an additional procedure after biopsy. Analysis with metaregression comparing native biopsies with transplant biopsies did not reveal that biopsy type (native kidney biopsy versus transplant kidney biopsy) was associated with the need for a blood transfusion or requirement of an additional intervention after biopsy., Conclusions: The development of perinephric hematoma after kidney biopsy is not an infrequent finding. The proportion of patients requiring blood transfusion or needing an additional intervention as a result of kidney biopsy in pediatric patients is significantly smaller., (Copyright © 2019 by the American Society of Nephrology.)