A Randomized, Double-Blind, Placebo-Controlled Trial of the Effects of Prophylactic Theophylline on Renal Function in Term Neonates With Perinatal Asphyxia

Jeník, Alejandro; Cernadas, José M. Ceriani; Gorenstein, Adriana; Ramirez, José A.; Vain, Néstor E.; Armadans, Marcelo; Ferraris, Jorge R.

doi:10.1542/peds.105.4.e45

Cited by 119 publications

(90 citation statements)

References 30 publications

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“…When related to the results of Gouyon and Guignard (4) with the same model, it appears that the nonspecific inhibition with theophylline was more likely to protect renal function in the neonatal period, as theophylline totally prevented the hypoxemia-induced vasomotor nephropathy in the newborn rabbit. Furthermore, theophylline significantly increased urine output and creatinine clearances in neonates with acute renal insufficiency due to respiratory distress syndrome (12) or perinatal asphyxia (13), as in diuretic-dependent critically ill children aged 1 wk to 17 y (14). As in the normoxic group, an increased renin release from the JG cells might have occurred after DPCPX administration, and adenosine-induced endothelin release in the kidney might also be involved.…”

Section: Map Heart Rate (Hr) Hematocrit (Htc) Plasma Protein Levmentioning

confidence: 90%

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Renal Effects of Adenosine A1-Receptor Blockade with 8-Cyclopentyl-1,3-Dipropylxanthine in Hypoxemic Newborn Rabbits

et al. 2003

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The key role of intrarenal adenosine in mediating the hypoxemic acute renal insufficiency in newborn rabbits has been well demonstrated using the nonspecific adenosine antagonist theophylline. The present study was designed to define the role of adenosine A 1 receptors during systemic hypoxemia by using the specific A 1 -receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Renal function parameters were assessed in 31 anesthetized and mechanically ventilated newborn rabbits. In normoxia, DPCPX infusion induced a significant increase in diuresis (ϩ44%) and GFR (ϩ19%), despite a significant decrease in renal blood flow (RBF) (Ϫ22%) and an increase in renal vascular resistance (RVR) (ϩ37%). In hypoxemic conditions, diuresis (Ϫ19%), GFR (Ϫ26%), and RBF (Ϫ35%) were decreased, whereas RVR increased (ϩ33%). DPCPX administration hindered the hypoxemia-induced decrease in GFR and diuresis. However, RBF was still significantly decreased (Ϫ27%), whereas RVR increased (ϩ22%). In all groups, the filtration fraction increased significantly. The overall results support the hypothesis that, in physiologic conditions, intrarenal adenosine plays a key role in regulating glomerular filtration in the neonatal period through preferential A 1 -mediated afferent vasoconstriction. During a hypoxemic stress, the A 1 -specific antagonist DPCPX only partially prevented the hypoxemiainduced changes, as illustrated by the elevated RVR and drop in RBF. These findings imply that the contribution of intrarenal adenosine to the acute adverse effects of hypoxemia might not be solely mediated via the A 1 receptor. Adenosine is ubiquitous in the kidney. Intrarenal adenosine vasoconstricts the preglomerular vessels via the A 1 receptors, while dilating the efferent arterioles via the A 2 receptors. It thus affects GFR as well as RBF and its distribution within the kidney. In addition to its vascular actions, intrarenal adenosine modulates renal mechanisms, including TGF, renin release, and the tubular handling of electrolytes and water. Intrarenal adenosine also appears to be an important hemodynamic mediator in some models of vasomotor nephropathy, such as those induced by intramuscular glycerol injection (1), contrast media (2), cisplatin (3), or hypoxemia (4).In animal models as in humans, hypoxemia can lead to functional renal insufficiency (5-7). In the newborn rabbit, acute normocapnic hypoxemia induces renal hypoperfusion with decreased GFR and RBF (4, 7-9). The underlying mechanism of this hypoxemia-induced vasomotor nephropathy still remains controversial. The chemoreceptor-mediated reflex and/or the activation of vasoactive factors such as angiotensin II (AII) (9), endothelin (10), nitric oxide (8), or bradykinin (11) have been suggested to play a role.We previously demonstrated that the administration of theophylline, a nonspecific antagonist to adenosine receptors, ameliorates the hypoxemia-induced renal hemodynamic changes seen in the newborn rabbit model (4). Moreover, in neonates with respiratory distress syndrome (12)

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Section: Map Heart Rate (Hr) Hematocrit (Htc) Plasma Protein Levmentioning

confidence: 90%

“…Moreover, in neonates with respiratory distress syndrome (12) or perinatal asphyxia (13), as in diuretic-dependent critically ill children (14), the use of theophylline improves diuresis and creatinine clearance. Specific adenosine receptor antagonists are now available for clinical use (15).…”

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confidence: 99%

Renal Effects of Adenosine A1-Receptor Blockade with 8-Cyclopentyl-1,3-Dipropylxanthine in Hypoxemic Newborn Rabbits

et al. 2003

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“…Several independent randomized studies in asphyxiated infants have shown that prophylactic theophylline, given early after birth, was associated with better kidney function. [70][71][72][73] As a result, the KDIGO guidelines recommend a single dose of theophylline for asphyxiated infants at risk for AKI. 44 Caution must be taken, as theophylline has some potentially harmful neurologic effects.…”

Section: Neonatal Cardiac Surgerymentioning

confidence: 99%

Neonatal Acute Kidney Injury

et al. 2015

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In recent years, there have been significant advancements in our understanding of acute kidney injury (AKI) and its impact on outcomes across medicine. Research based on single-center cohorts suggests that neonatal AKI is very common and associated with poor outcomes. In this state-of-the-art review on neonatal AKI, we highlight the unique aspects of neonatal renal physiology, definition, risk factors, epidemiology, outcomes, evaluation, and management of AKI in neonates. The changes in renal function with gestational and chronologic age are described. We put forth and describe the neonatal modified Kidney Diseases: Improving Global Outcomes AKI criteria and provide the rationale for its use as the standardized definition of neonatal AKI. We discuss risk factors for neonatal AKI and suggest which patient populations may warrant closer surveillance, including neonates ,1500 g, infants who experience perinatal asphyxia, near term/ term infants with low Apgar scores, those treated with extracorporeal membrane oxygenation, and those requiring cardiac surgery. We provide recommendations for the evaluation and treatment of these patients, including medications and renal replacement therapies. We discuss the need for long-term follow-up of neonates with AKI to identify those children who will go on to develop chronic kidney disease. This review highlights the deficits in our understanding of neonatal AKI that require further investigation. In an effort to begin to address these needs, the Neonatal Kidney Collaborative was formed in 2014 with the goal of better understanding neonatal AKI, beginning to answer critical questions, and improving outcomes in these vulnerable populations.

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“…3 Jenik dkk melaporkan pemberian teofolin 8 mg/kgbb yang diberikan beberapa jam setelah lahir pada neonatus cukup bulan dengan asfiksia berat secara bermakna dapat menurunkan kreatinin serum dan b2-mikroglobulin urin, serta terjadinya peningkatan klirens kreatinin. 25 …”

Section: Dampak Terhadap Ginjalunclassified

Gangguan Fungsi Multi Organ pada Bayi Asfiksia Berat

Manoe¹,

Amir²

2016

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AIndonesia mempunyai 200 juta penduduk dengan angka kelahiran 2,5%/tahun sehingga diperkirakan terdapat 5 juta kelahiran per tahun. Jika angka kejadian asfiksia 3-5% dari seluruh kelahiran, diperkirakan 250 ribu bayi asfiksia lahir pertahun. 4 Di Bagian Ilmu Kesehatan Anak FKUI-RSCM pada tahun 2000 didapatkan 6,3% bayi asfiksia dari seluruh kelahiran, 2,1% diantaranya lahir dengan asfiksia berat.5 Pelbagai faktor pada ibu dan bayi berperan sebagai faktor risiko asfiksia perinatal. 6Penilaian perinatal terhadap faktor risiko dan penanganan perinatal yang baik pada kehamilan risiko tinggi sangat mutlak pada asfiksia perinatal. Apabila komplikasi asfiksia sudah terjadi maka diperlukan pendekatan multidisiplin untuk mencegah kerusakan yang sudah terjadi agar tidak bertambah berat. 7,8 Tulisan ini bertujuan untuk membahas dampak asfiksia pada sistem susunan saraf pusat, jantung, ginjal, gastrointestinal, darah dan paru, sehingga penanganan asfiksia pada bayi baru lahir akan lebih baik. sfiksia perinatal masih merupakan penyebab utama morbiditas dan mortalitas pada bayi baru lahir baik di negara berkembang maupun di negara maju.1,2 Di negara maju angka kejadian asfiksia berkisar antara 1-1,5 % dan berhubungan dengan masa gestasi dan berat lahir.3 Di negara berkembang angka kejadian bayi asfiksia lebih tinggi dibandingkan di negara maju karena pelayanan antenatal yang masih kurang memadai. Sebagian besar bayi asfiksia tersebut tidak memperoleh penanganan yang adekuat sehingga banyak diantaranya meninggal. 1,4Asfiksia perinatal masih merupakan masalah baik di negara berkembang maupun di negara maju dan menyebabkan kematian sebesar 20% dari bayi baru lahir. Keadaan hipoksia dan iskemia yang terjadi akibat afiksia akan menimbulkan gangguan pada berbagai fungsi organ. Proses terjadinya gangguan bergantung pada berat dan lamanya hipoksia terjadi dan berkaitan dengan proses reoksigenisasi jaringan setelah proses hipoksia tersebut berlangsung. Faktor risiko terjadinya asfiksia pada bayi baru lahir terdiri dari faktor ibu, faktor janin dan faktor persalinan/kelahiran. Hal ini penting, karena dengan pengenalan faktor risiko tersebut maka persiapan resusitasi bayi dapat dilakukan. Beberapa organ tubuh yang akan mengalami disfungsi akibat asfiksia perinatal adalah otak, paru, hati, ginjal, saluran cerna dan sistem darah. Dampak jangka panjang bayi yang mengalami asfiksia berat antara lain ensefalopati hipoksik-iskemik, iskemia miokardial transien, insufisiensi trikuspid, nekrosis miokardium, gagal ginjal akut, nekrosis tubular akut, enterokolitis, SIADH (syndrome inappropriate anti diuretic hormone) kerusakan hati, Koagulasi intra-vaskular diseminata (KID), perdarahan dan edem paru, penyakit membran hialin HMD sekunder dan aspirasi mekonium.Kata kunci: asfiksia, hipoksia, iskemia, ensefalopati, bayi baru lahir.

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A Randomized, Double-Blind, Placebo-Controlled Trial of the Effects of Prophylactic Theophylline on Renal Function in Term Neonates With Perinatal Asphyxia

Abstract: Our data suggest that prophylactic theophylline, given early after birth, has beneficial effects on reducing the renal dysfunction in asphyxiated full-term infants. (ABSTRACT TRUNCATED)

Cited by 119 publications

References 30 publications

Renal Effects of Adenosine A1-Receptor Blockade with 8-Cyclopentyl-1,3-Dipropylxanthine in Hypoxemic Newborn Rabbits

Renal Effects of Adenosine A1-Receptor Blockade with 8-Cyclopentyl-1,3-Dipropylxanthine in Hypoxemic Newborn Rabbits

Neonatal Acute Kidney Injury

Gangguan Fungsi Multi Organ pada Bayi Asfiksia Berat

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