Recurrent Acute Kidney Injury Research Articles

463 - Recurrent neonatal acute kidney injury: Incidence, predictors, and outcomes in the neonatal intensive care unit

463 - Recurrent neonatal acute kidney injury: Incidence, predictors, and outcomes in the neonatal intensive care unit

Long-term outcomes of COVID-19 survivors with hospital AKI: association with time to recovery from AKI.

Although coronavirus disease 2019 (COVID-19) patients who develop in-hospital acute kidney injury (AKI) have worse short-term outcomes, their long-term outcomes have not been fully characterized. We investigated 90-day and 1-year outcomes after hospital AKI grouped by time to recovery from AKI. This study consisted of 3296 COVID-19 patients with hospital AKI stratified by early recovery (<48hours), delayed recovery (2-7days) and prolonged recovery (>7-90days). Demographics, comorbidities and laboratory values were obtained at admission and up to the 1-year follow-up. The incidence of major adverse cardiovascular events (MACE) and major adverse kidney events (MAKE), rehospitalization, recurrent AKI and new-onset chronic kidney disease (CKD) were obtained 90-days after COVID-19 discharge. The incidence of hospital AKI was 28.6%. Of the COVID-19 patients with AKI, 58.0% experienced early recovery, 14.8% delayed recovery and 27.1% prolonged recovery. Patients with a longer AKI recovery time had a higher prevalence of CKD (P<.05) and were more likely to need invasive mechanical ventilation (P<.001) and to die (P<.001). Many COVID-19 patients developed MAKE, recurrent AKI and new-onset CKD within 90days, and these incidences were higher in the prolonged recovery group (P<.05). The incidence of MACE peaked 20-40days postdischarge, whereas MAKE peaked 80-90days postdischarge. Logistic regression models predicted 90-day MACE and MAKE with 82.4±1.6% and 79.6±2.3% accuracy, respectively. COVID-19 survivors who developed hospital AKI are at high risk for adverse cardiovascular and kidney outcomes, especially those with longer AKI recovery times and those with a history of CKD. These patients may require long-term follow-up for cardiac and kidney complications.

Epigenetic memory contributing to the pathogenesis of AKI-to-CKD transition.

Epigenetic memory, which refers to the ability of cells to retain and transmit epigenetic marks to their daughter cells, maintains unique gene expression patterns. Establishing programmed epigenetic memory at each stage of development is required for cell differentiation. Moreover, accumulating evidence shows that epigenetic memory acquired in response to environmental stimuli may be associated with diverse diseases. In the field of kidney diseases, the “memory” of acute kidney injury (AKI) leads to progression to chronic kidney disease (CKD); epidemiological studies show that patients who recover from AKI are at high risk of developing CKD. The underlying pathological processes include nephron loss, maladaptive epithelial repair, inflammation, and endothelial injury with vascular rarefaction. Further, epigenetic alterations may contribute as well to the pathophysiology of this AKI-to-CKD transition. Epigenetic changes induced by AKI, which can be recorded in cells, exert long-term effects as epigenetic memory. Considering the latest findings on the molecular basis of epigenetic memory and the pathophysiology of AKI-to-CKD transition, we propose here that epigenetic memory contributing to AKI-to-CKD transition can be classified according to the presence or absence of persistent changes in the associated regulation of gene expression, which we designate “driving” memory and “priming” memory, respectively. “Driving” memory, which persistently alters the regulation of gene expression, may contribute to disease progression by activating fibrogenic genes or inhibiting renoprotective genes. This process may be involved in generating the proinflammatory and profibrotic phenotypes of maladaptively repaired tubular cells after kidney injury. “Priming” memory is stored in seemingly successfully repaired tubular cells in the absence of detectable persistent phenotypic changes, which may enhance a subsequent transcriptional response to the second stimulus. This type of memory may contribute to AKI-to-CKD transition through the cumulative effects of enhanced expression of profibrotic genes required for wound repair after recurrent AKI. Further understanding of epigenetic memory will identify therapeutic targets of future epigenetic intervention to prevent AKI-to-CKD transition.

Factors associated with acute kidney injury among patients with cancer treated with immune checkpoint inhibitor therapy: A population-based study.

2584 Background: Cancer immune checkpoint inhibitor (ICI) therapy may be associated with kidney immune-related adverse events (IRAEs) and other causes of acute kidney injury (AKI). In clinical trials, the frequency of AKI events was uncommon, however, further real-world study is warranted. Methods: We evaluated the proportion of AKI events among patients with advanced cancer (bladder, head and neck, lung, kidney and malignant melanoma) treated with ICI therapy in Ontario, Canada from 2012 - 2018. AKI was defined by a rise in the concentration of serum creatinine as per Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A multivariable regression model was used to identify predictors of AKI while accounting for the competing risk of death. Results: A total of 4,380 patients received ICI therapy. In follow-up, 1,283 (29%) had recorded AKI event (any stage AKI) and 289 (7%) had a severe AKI event (≥ stage 2). Median time to AKI was 6 months (Interquartile Range 2-16 months) and ≤ 1 % of patients received dialysis therapy. Within 30 days of any observed AKI event, 853 (58%) discontinued ICI therapy, 372 (29%) were hospitalized and 266 (21%) died. Mortality was significantly higher among patients who experiencing a severe AKI event (≥ stage 2) as compared to patients with a less severe AKI event (stage 1) or no observed AKI event. Among patients alive at 30 days following an AKI event, 14% received an outpatient corticosteroid or immunosuppressive therapy prescription, 7% had a visit with a nephrologist. Characteristics associated with a higher risk of AKI included female sex, bladder or kidney cancer (reference malignant melanoma), history of hypertension or diabetes, higher Charlson comorbidity score, a baseline estimated glomerular filtration rate less than 30 mL/min/1.73 m2, or outpatient prescription for either a proton pump inhibitor or non-steroidal anti-inflammatory drug. Among patients with an AKI event and treatment discontinuation, re-challenge of ICI therapy was infrequent (16%) with a significant risk of a recurrent AKI event (57%). Conclusions: In a population-based study among patients with cancer receiving ICI therapy, the rate of AKI was common (29%) but severe AKI was less frequent (7%). Rates of ICI discontinuation, hospitalization and death are substantial following an AKI event. Kidney function should be monitored carefully among patients undergoing ICI therapy who have common risk factors for developing renal disease. Nephrology consultation may be optimized among patients who develop a severe AKI event, especially among individuals who are considered for ICI therapy re-challenge.

Risk factors, outcomes, and predictors of resolution of acute kidney injury in children with diabetic ketoacidosis.

Acute kidney injury (AKI) is a common complication in patients with diabetic ketoacidosis (DKA) (incidence 35-77%). AKI evolution during DKA treatment/recovery is poorly understood. Our aim was to assess children with DKA for prevalence, short-term kidney outcomes, severity, and predictors of AKI development and resolution. This retrospective cohort study included children aged 2-14years admitted with DKA between January 2016 and May 2020 in a Saudi tertiary care hospital. We defined AKI as an increase in serum creatinine of > 1.5 times baseline or > 3mg/dL (26mmol/L) within 48h. Of 213 patients admitted with DKA, 172 (80.75%) developed AKI: stage 1 in 83 (38.96%), stage 2 in 86 (40.37%), and stage 3 in 3 (1.4%). No patient required dialysis. Multivariate analysis showed an increased risk of developing AKI with male gender (OR = 2.85) and lower serum bicarbonate (OR = 0.83) when adjusted for initial heart rate, hematocrit, new onset diabetes, and recurrent AKI. The mean time to AKI resolution was 13.21 ± 6.78h. Factors leading to prolonged recovery from AKI in linear regression analysis were older age (B coefficient = 0.44, p = 0.01), recurrent DKA episodes (B coefficient = 3.70, p value 0.003), increased acidosis severity (B coefficient = - 0.44, p = 0.04), increased time to anion gap normalization (B coefficient = 0.44, p = 0.019), and increased initial glucose (B coefficient = 0.01, p = 0.011). In our cohort, AKI is a common, but mostly transient complication in children presenting with DKA, and its severity is associated with longer intensive care stays and time for acidosis resolution. AKI was associated with male gender, and lower serum bicarbonate. Proper consideration of such risk factors is needed for AKI assessment and management in future DKA clinical practice guidelines. A higher resolution version of the Graphical abstract is available as Supplementary information.

Experimental Aristolochic Acid Nephropathy: A Relevant Model to Study AKI-to-CKD Transition.

Aristolochic acid nephropathy (AAN) is a progressive tubulointerstitial nephritis caused by the intake of aristolochic acids (AA) contained in Chinese herbal remedies or contaminated food. AAN is characterized by tubular atrophy and interstitial fibrosis, characterizing advanced kidney disease. It is established that sustained or recurrent acute kidney injury (AKI) episodes contribute to the progression of CKD. Therefore, the study of underlying mechanisms of AA-induced nephrotoxicity could be useful in understanding the complex AKI-to-CKD transition. We developed a translational approach of AKI-to-CKD transition by reproducing human AAN in rodent models. Indeed, in such models, an early phase of acute tubular necrosis was rapidly followed by a massive interstitial recruitment of activated monocytes/macrophages followed by cytotoxic T lymphocytes, resulting in a transient AKI episode. A later chronic phase was then observed with progressive tubular atrophy related to dedifferentiation and necrosis of tubular epithelial cells. The accumulation of vimentin and αSMA-positive cells expressing TGFβ in interstitial areas suggested an increase in resident fibroblasts and their activation into myofibroblasts resulting in collagen deposition and CKD. In addition, we identified 4 major actors in the AKI-to-CKD transition: (1) the tubular epithelial cells, (2) the endothelial cells of the interstitial capillary network, (3) the inflammatory infiltrate, and (4) the myofibroblasts. This review provides the most comprehensive and informative data we were able to collect and examines the pending questions.

FC 129: Stopping versus Continuing Renin–Angiotensin System Inhibitors After Acute Kidney Injury and Adverse Clinical Outcomes: An Observational Study From Routine Care Data

Abstract BACKGROUND AND AIMS The risk–benefit ratio of continuing with renin–angiotensin system inhibitors (RASi) after an episode of acute kidney injury (AKI) is unclear. While stopping RASi may prevent recurrent AKI or hyperkalaemia, it may deprive patients of the cardiovascular benefits of using RASi. METHOD We analysed outcomes of long-term RASi users experiencing AKI (stage 2 or 3, or clinically coded) during hospitalization in Stockholm, Sweden, during 2007–2018. We compared stopping RASi within 3 months after discharge with continuing. The primary study outcome was the composite of all-cause mortality, myocardial infarction and stroke. Recurrent AKI was our secondary outcome, and we considered hyperkalaemia as a positive control outcome. Propensity score overlap weighted Cox models were used to estimate hazard ratios, balancing 75 confounders. Weighted absolute risk differences (ARD) were also determined. RESULTS We included 10 165 individuals, of whom 4429 stopped and 5736 continued RASi, with a median follow-up of 2.3 years. Median age was 78 years, 45% were women, and median kidney function before the index episode of AKI was 55 mL/min/1.73 m2. After weighting, those who stopped had an increased risk [HR, 95% confidence interval (95% CI)] of the composite of death, myocardial infarction and stroke (1.13, 1.07–1.19; ARD 3.7, 95% CI 2.6–4.8) compared with those who continued, a similar risk of recurrent AKI (0.94, 0.84–1.05), and a decreased risk of hyperkalaemia (0.79, 0.71–0.88). CONCLUSION Stopping RASi use among survivors of moderate-to-severe AKI was associated with a similar risk of recurrent AKI, but higher risk of the composite of death, myocardial infarction and stroke.

Recurrent acute kidney injury in elderly patients is common and associated with 1-year mortality.

Acute kidney injury (AKI) is common among elderly patients after a first hospitalized AKI. Patients who recover are at risk for recurrence, but recurrent geriatric AKI is not well-studied. This was a retrospective, 12-month cohort study using data from the National Clinical Research Center for Geriatric Diseases. Recurrent AKI was defined as a new spontaneous rise of ≥ 0.3mg/dl (≥ 26.5µmol/L) within 48h or a 50% increase in serum creatinine (Scr) from the baseline within 7days after the previous AKI episode. The outcome measured was 12-month mortality. Among 1711 study patients, 652 developed AKI. Of the 429 AKI survivors in whom recovery could be assessed, 314 patients recovered to their baseline renal function, and 115 patients developed chronic kidney disease (CKD). Of the group that recovered renal function, 90 patients (28.7%) subsequently developed recurrent AKI, while 224 (71.3%) did not. Of the 429 survivors with AKI, 103 patients (24.0%) died within 12months. Multivariate logistic regression analysis revealed that recurrent AKI was significantly associated with coronary disease (odds ratio [OR = 2.008; 95% confidence interval [CI] 1.024-3.938; P = 0.042), a need for mechanical ventilation (OR = 2.265; 95% CI 1.267-4.051; P = 0.006) and high blood urea nitrogen levels (OR = 1.036; 95% CI 1.002-1.072; P = 0.040) at the first AKI event. Kaplan-Meier curves showed the 12-month survival of patients with non-recurrent AKI was better than that of patients with CKD, and survival of patients with recurrent AKI was worse than that of patients with CKD (log rank P < 0.001). In the multivariate Cox regression analysis, mortality at 12month was higher in the patient with recurrent AKI as compared with those with a single episode (HR = 3.375; 95% CI 2.241-5.083; P < 0.001). Recurrent AKI is common among elderly patients who recovered their renal function post-AKI and is associated with significantly higher 12-month mortality compared with CKD patients.

Predicting Post-Heart Transplant Composite Renal Outcome Risk in Adults: A Machine Learning Decision Tool

Predicting Post-Heart Transplant Composite Renal Outcome Risk in Adults: A Machine Learning Decision Tool

Hypouricaemia and acute kidney injury: a hereditary condition should be considered.

I read with interest the case report by Tadokoro et al.1 about a 17-year-old woman, presumably of Japanese ethnicity, who presented with acute kidney injury (AKI) following a basketball game. In view of the clinical course and computed tomography images, a diagnosis of exercise-induced acute kidney injury (EIAKI) was made; notably, uric acid (UA) was 1.3 mg/dl on admission. Although the association of EIAKI with hypouricaemia (by convention defined as a serum urate concentration of <2 mg/dl)2 was duly acknowledged, I was surprised that the authors did not elaborate on the potential causes of this finding. A UA level of 1.3 mg/dl in the context of AKI is highly unusual and should alert the clinician to the possibility of an underlying defect in renal UA reabsorption. Specifically, renal hypouricaemia (RHUC), a genetically heterogenous disorder caused by mutations in two major renal tubular UA transporters (URAT1, encoded by SLC22A12, and GLUT9, encoded by SLC2A9), predisposes affected individuals to kidney stones and recurrent AKI, the latter typically provoked by exercise.3 Although certainly qualifying as an orphan disease, the prevalence of RHUC varies significantly and is reasonably common in certain Asian regions, particularly in Japan, where the estimated prevalence reaches 0.5% in the general population.4 The pathophysiology of EIAKI is incompletely understood. UA is a powerful antioxidant and hypouricaemia may trigger an oxidative imbalance during exercise; resultant renovascular spasm shares similarities with ischaemia-reperfusion injury.2,3

Ultrasonography in Acute Kidney Injury.

Advances in the use of ultrasonography can enhance our ability to better characterize acute kidney injury (AKI). AKI is a clinical syndrome characterized by a rapid decrease in kidney excretory function with the accumulation of products of nitrogen metabolism and other clinically unmeasured waste products, and may proceed to include clinical manifestations including decreased urine output, development of metabolic acidosis, and electrolyte abnormalities [1]. The Kidney Disease Improving Global Outcomes (KDIGO) criteria defines AKI (Table 1). Staging severity of AKI guides the physician in respect to medical management and prognosis. The overall incidence of AKI is around 20% of patients hospitalized worldwide, and around 50% in intensive care unit (ICU) patients [2, 3]. AKI has been found to have increasing morbidity and mortality, no matter the cause of admission, as well as an in-hospital mortality of close to 50% [4]. In a large study of 8 ICUs over 8 years, Kellum et al. found that AKI was associated with increasing mortality rate with worsening AKI stage. A decrease in urine output alone, without an increase in serum creatinine, was associated with decreased 1-year survival [5]. Recurrent AKI has also been associated with increased mortality, further demonstrating the importance of detecting, monitoring, and diagnosing AKI [6].

Stopping versus continuing renin–angiotensin–system inhibitors after acute kidney injury and adverse clinical outcomes: an observational study from routine care data

ABSTRACTBackgroundThe risk–benefit ratio of continuing with renin–angiotensin system inhibitors (RASi) after an episode of acute kidney injury (AKI) is unclear. While stopping RASi may prevent recurrent AKI or hyperkalaemia, it may deprive patients of the cardiovascular benefits of using RASi.MethodsWe analysed outcomes of long-term RASi users experiencing AKI (stage 2 or 3, or clinically coded) during hospitalization in Stockholm and Sweden during 2007–18. We compared stopping RASi within 3 months after discharge with continuing RASi. The primary study outcome was the composite of all-cause mortality, myocardial infarction (MI) and stroke. Recurrent AKI was our secondary outcome and we considered hyperkalaemia as a positive control outcome. Propensity score overlap weighted Cox models were used to estimate hazard ratios (HRs), balancing 75 confounders. Weighted absolute risk differences (ARDs) were also determined.ResultsWe included 10 165 individuals, of whom 4429 stopped and 5736 continued RASi, with a median follow-up of 2.3 years. The median age was 78 years; 45% were women and median kidney function before the index episode of AKI was 55 mL/min/1.73 m2. After weighting, those who stopped had an increased risk [HR, 95% confidence interval (CI)] of the composite of death, MI and stroke [1.13, 1.07–1.19; ARD 3.7, 95% CI 2.6–4.8] compared with those who continued, a similar risk of recurrent AKI (0.94, 0.84–1.05) and a decreased risk of hyperkalaemia (0.79, 0.71–0.88).DiscussionStopping RASi use among survivors of moderate-to-severe AKI was associated with a similar risk of recurrent AKI, but higher risk of the composite of death, MI and stroke.

Recurrent acute kidney injury in preterm neonates is common and associated with worse outcomes and higher mortality.

Acute kidney injury (AKI) in preterm neonates is associated with poor outcomes that may worsen in the setting of recurrent episodes of AKI. This study defines and studies the incidence, risk factors, and outcomes of recurrent AKI (rAKI). Retrospective chart review of the neonates born at a gestational age of ≤28 weeks admitted to the neonatal intensive care unit (NICU) between January 2014 and December 2018. We identified AKI based on the serum creatinine (Scr) concentrations using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. rAKI was defined as the occurrence of AKI after Scr from the prior AKI had returned to baseline. Forty-nine of the 205 (24%) preterm neonates developed rAKI. An earlier diagnosis (<7 days old) and a higher KDIGO stage (stage 3) at the initial episode of AKI was associated with rAKI (p = 0.03). Preterm neonates with rAKI had higher mortality as compared to those with a single episode of AKI (sAKI) (adjustedodds ratio(aOR) 4.55, 95% confidence interval (CI), 1.12-18.51). Length of stay (LOS) was longer among neonates with rAKI as compared to those with sAKI by 36 days (95% CI 24.9-47.1). Recurrent AKI in preterm neonates was associated with earlier episodes and higher KDIGO stage of the initial AKI episode. Neonates with rAKI had higher mortality and longer LOS compared to those with sAKI. Definition and study of the incidence of rAKI and its associated outcomes among preterm neonates. Recurrent AKI is common among preterm neonates and may contribute to worse outcomes for premature neonates in the NICU. Early recognition of the risk factors for AKI, and effective management of initial AKI and early phase of recurrent AKI may improve outcomes of these preterm neonates.

The Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II Receptor Blockers on Clinical Outcomes of Acute Kidney Disease Patients: A Systematic Review and Meta-Analysis.

Background: Acute kidney injury (AKI) may increase the risk of chronic kidney disease (CKD), development of end-stage renal disease (ESRD), and mortality. However, the impact of exposure to angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (ACEi/ARB) in patients experiencing AKI/acute kidney disease (AKD) is still unclear. Methods: In this systematic review, we searched all relevant studies from PubMed, Embase, Cochrane, Medline, Collaboration Central Register of Controlled Clinical Trials, Cochrane Systematic Reviews, and ClinicalTrials.gov until July 21, 2020. We evaluated whether the exposure to ACEi/ARB after AKI onset alters recovery paths of AKD and impacts risks of all-cause mortality, recurrent AKI, or incident CKD. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. Results: A total of seven articles, involving 70,801 patients, were included in this meta-analysis. The overall patient mortality rate in this meta-analysis was 28.4%. Among AKI patients, all-cause mortality was lower in ACEi/ARB users than in ACEi/ARB nonusers (log odds ratio (OR) −0.37, 95% confidence interval (CI): −0.42–−0.32, p < 0.01). The risk of recurrent adverse kidney events after AKI was lower in ACEi/ARB users than in nonusers (logOR −0.25, 95% CI: −0.33–−0.18, p < 0.01). The risk of hyperkalemia was higher in ACEi/ARB users than in nonusers (logOR 0.43, 95% CI: 0.27–0.59, p < 0.01). Patients with continued use of ACEi/ARB after AKI also had lower mortality risk than those prior ACEi/ARB users but who did not resume ACEi/ARB during AKD (logOR −0.36, 95% CI: −0.4–−0.31, p < 0.01). Conclusions: Exposure to ACEi/ARB after AKI is associated with lower risks of all-cause mortality, recurrent AKI, and progression to incident CKD. Patients with AKI may have a survival benefit by continued use of ACEi/ARB; however, a higher incidence of hyperkalemia associated with ACEi/ARB usage among these patients deserves close clinical monitoring.

Recurrent acute kidney injury and rhabdomyolysis: Questions.

Recurrent acute kidney injury and rhabdomyolysis: Questions.

Recurrent acute kidney injury and rhabdomyolysis: Answers.

Recurrent acute kidney injury and rhabdomyolysis: Answers.

Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Therapeutic Strategy for Acute Kidney Injury.

Acute kidney injury (AKI) is a common and potential life-threatening disease in patients admitted to hospital, affecting 10%–15% of all hospitalizations and around 50% of patients in the intensive care unit. Severe, recurrent, and uncontrolled AKI may progress to chronic kidney disease or end-stage renal disease. AKI thus requires more efficient, specific therapies, rather than just supportive therapy. Mesenchymal stem cells (MSCs) are considered to be promising cells for cellular therapy because of their ease of harvesting, low immunogenicity, and ability to expand in vitro. Recent research indicated that the main therapeutic effects of MSCs were mediated by MSC-derived extracellular vesicles (MSC-EVs). Furthermore, compared with MSCs, MSC-EVs have lower immunogenicity, easier storage, no tumorigenesis, and the potential to be artificially modified. We reviewed the therapeutic mechanism of MSCs and MSC-EVs in AKI, and considered recent research on how to improve the efficacy of MSC-EVs in AKI. We also summarized and analyzed the potential and limitations of EVs for the treatment of AKI to provide ideas for future clinical trials and the clinical application of MSC-EVs in AKI.

MO427SAFE USE OF ALLOPURINOL TO TREAT ACUTE URIC ACID NEPHROPATHY IN PREGNANCY: A CASE REPORT

Abstract Introduction Acute uric acid nephropathy (UAN) is characterized by acute kidney injury (AKI) due to uric acid crystal precipitation within the distal tubules and collecting ducts. We present a young woman, with a history of hyperuricaemia, who was treated with allopurinol for acute UAN during her first pregnancy. She also continued allopurinol treatment during her second pregnancy for prevention of further acute UAN. To the author’s knowledge, this is the first case report of biopsy-confirmed acute UAN during pregnancy. Case report A 20 year old woman, who was 13 weeks pregnant, was admitted with AKI. Past medical history included chronic kidney disease (CKD) and gout since the age of 17. She had an extensive family history of CKD and gout (without diagnosis, despite genetic testing). She had been on daily allopurinol 300mg, but this was stopped 8 weeks prior by her rheumatology team due to concerns about teratogenicity. At that time serum creatinine was at her baseline of 100 μmol/L (normal range 50-120 μmol/L) and serum uric acid had been 740 μmol/L (normal range 140-360 μmol/L). On admission, she felt well and was euvolemic. Serum creatinine was now 352 μmol/L and her serum uric acid level was 1720 μmol/L, with an elevated urine uric acid to creatinine ratio of 1.1. She underwent renal biopsy, which showed significant deposition of uric acid crystals in the renal tubules, confirming a diagnosis of acute UAN. She was given intravenous fluids. The uncertainties of allopurinol use in pregnancy were discussed with her, and she was restarted on allopurinol 200 mg daily. Over the next 3 weeks, serum uric acid decreased to 470 μmol/L and serum creatinine to 116 μmol/L. She was maintained on allopurinol during her pregnancy and delivered a healthy baby girl. She was advised against further pregnancies due to increased risk of maternal and fetal complications. However, three years later she presented at 15 weeks’ gestation. After a discussion regarding the potential teratogenic effects of allopurinol versus the risk of recurrent severe AKI due to acute UAN if it was again discontinued, she chose to continue allopurinol. The pregnancy proceeded without complication. Her daughters are now 8 and 5 years old. They do not have any congenital malformations, though both have mild to moderate learning difficulties. Discussion Allopurinol is approved for the treatment of hyperuricaemia outside of pregnancy, but given it interrupts purine synthesis there is a biologically plausible concern regarding teratogenicity. However, in our patient with long-standing hyperuricaemia it was the discontinuation of allopurinol that precipitated AKI due to the resultant crystal formation when serum uric acid reached very high levels. Biopsy confirmation of acute UAN was vital in this case, given the possibility of missing an alternative diagnosis and the risks of giving empirical allopurinol therapy. Once the diagnosis for her severe AKI was confirmed, it was clear our patient would benefit from uric acid lowering therapy. Our patient had two healthy girls despite using allopurinol from week 16 in her first pregnancy and throughout her second pregnancy. Unfortunately, both girls have mild to moderate learning needs, though it is unprovable whether allopurinol was causative as no study has followed up long term outcomes after foetal exposure during pregnancy.

Hypercalcemia: A Metabolic Complication of an AIDS-Defining Illness

Abstract Background: Hypercalcemia may result from the activation of macrophages in granulomatous diseases with increased production of 1,25 dihydroxyvitamin D/calcitriol. Its occurrence in patients with human immunodeficiency virus-1 (HIV-1) infection may be atypical and signal major changes in immune status. We report on a patient with acquired immunodeficiency syndrome (AIDS) presenting with new-onset hypercalcemia after months of treatment for mycobacterium avium complex (MAC) infection and normal calcitriol levels. Clinical Case: A 37-year-old man on treatment for HIV-1 and disseminated MAC infection presented to the hospital 6 months after initial diagnosis with worsening headache, cough, and abdominal pain. On arrival he was afebrile and without palpable lymphadenopathy. He was found to have a high serum calcium (13.4 mg/dL, n 8.6–10.6 mg/dL) and acute kidney injury (AKI) (creatinine 4 mg/dL, n 0.6–1.25 mg/dL). His CD4 count had increased from 24 at time of diagnosis to 162 cells/μL (n 410–1,590 cells/μL); his HIV viral load was undetectable. Workup for hypercalcemia revealed an elevated phosphorus (5.2 mg/dL, n 2.5–5.0 mg/dL), low 25-OH vitamin D level (&amp;lt;13 ng/mL, n 25–80 ng/dL), low PTH (4.8 pg/mL, n 12–88 pg/mL), and calcitriol level of 31.4 pg/mL, n 19.9–73.3 pg/mL). Additional tests, including serum electrophoresis, thyroid stimulating hormone, and parathyroid hormone-related peptide levels, were unremarkable. The patient was diagnosed with hypercalcemia secondary to dysregulated calcitriol production in the setting of disseminated MAC and possible immune reconstitution. Hypercalcemia resolved with hydration and prednisone 20 mg daily. Patient was discharged with an 8-day prednisone taper, but readmitted to the hospital 3 weeks later with recurrent hypercalcemia (13.8 mg/dL) and AKI. Urine calcium was found to be elevated (484 mg/24 hours, n100-300 mg/24 hours) and repeat calcitriol was 53.6 pg/ml. Patient was restarted on prednisone 40 mg daily with normalization of calcium within 5 days (calcium 10.3 mg/dL). Conclusion: Hypercalcemia due to increased calcitriol production in the setting of MAC infection, an AIDS-defining illness, may occur months after initiation of effective antibiotic and antiviral therapy and could represent a manifestation of immune reconstitution. The deleterious effects of excess calcitriol may be present even in patients with chronic vitamin D deficiency and a calcitriol level that inappropriately remains within the normal range.

Acute Kidney Injury in a Patient with Trisomy 21.

1. Hannah S. Kim, MD* 2. Francesca Costigliolo, MD† 3. Serena Bagnasco, MD† 4. Jeffrey Fadrowski, MD, MHS* 5. Rebecca L. Ruebner, MD, MSCE* 1. *Division of Pediatric Nephrology and 2. †Division of Pathology, Johns Hopkins University, Baltimore, MD A 5-year-old former 34-week girl with trisomy 21, hypothyroidism, and obstructive sleep apnea presents to the emergency department with a chief complaint of fever. She initially presented to her pediatrician 3 weeks earlier with sore throat and was diagnosed as having group A streptococcal pharyngitis. She completed 10 days of amoxicillin with resolution of sore throat. Now for the past 3 days she has had fever, chest pain, decreased enteral intake, and emesis. Review of systems is negative for diarrhea, gross hematuria, dysuria, polyuria, polydipsia, edema, weight loss, rash, arthralgia, arthritis, oral ulcers, epistaxis, and hemoptysis. She has had normal growth. She takes levothyroxine and took several doses of ibuprofen for fever over the past several weeks. There is no family history of kidney disease. She had no recent travel or sick contacts. On physical examination her weight is 45.2 lb (20.5 kg) (65th percentile); height, 46.1 in (117 cm) (62% percentile); temperature, 100.8°F (38.2°C); heart rate, 110 beats/min; respiratory rate, 24 breaths/min; oxygen saturation, 100% on room air; and blood pressure, 92/42 mm Hg (systolic 31st and diastolic 9th percentiles for age and sex). There is no pharyngeal injection or exudate. She appears well-hydrated, including moist mucous membranes. Lungs are clear to auscultation. Her abdomen is soft, nontender, and nondistended. There is no edema, and she has brisk capillary refill. She has no rash or joint swelling, erythema, or warmth. Laboratory evaluation includes a white blood cell count of 15,310/µL (15.31×109/L) with 83.6% neutrophils and 0.8% bands; hemoglobin …