920 SECTION VII Pediatric Critical Care Renal these agents are considerably more expensive, and the difference in nephrotoxicity is less pronounced in children versus adults 143,144 The introduction o[.]
920 S E C T I O N V I I Pediatric Critical Care: Renal these agents are considerably more expensive, and the difference in nephrotoxicity is less pronounced in children versus adults.143,144 The introduction of alternative antifungal agents—such as itraconazole, voriconazole, and caspofungin—has largely supplanted the use of amphotericin B in high-risk patients with renal impairment However, amphotericin B continues to be used widely in patients with normal renal function because of its relatively low cost and broad spectrum of activity.145 Given the presence of many underlying risk factors for nephrotoxicity in critically ill patients, it is recommended that amphotericin B should be avoided in this patient population if alternative therapies are available When it is used, sodium loading with IV hydration is recommended to attenuate vasoconstrictive effects; longer infusion times should also be considered Renal function and serum electrolytes (specifically potassium) should be monitored during treatment, especially in premature infants pathogenesis of CNI nephrotoxicity.154 Experimental models of acute cyclosporine A (CSA) toxicity revealed that CSA administration is associated with clinical manifestations of CNI-induced afferent and efferent arteriolar vasoconstriction, which results in a significant reduction of renal plasma flow and GFR.155,156 The precise mechanism by which CSA induces renal vasoconstriction has not been established clearly Results from several studies indicate that vascular dysfunction induced by CSA results from an increase in vasoconstrictor factors that include endothelin, thromboxane, and angiotensin II, as well as a reduction of vasodilator factors such as prostacyclin and nitric oxide.157 They include vasoconstriction glomerular arterioles, which leads to reduction of GFR and ultimately results in hyperkalemia, hypertension, renal tubular acidosis, increased resorption of sodium, and oliguria The acute adverse effects of CNIs on renal hemodynamics are thought to be directly related to the CSA or tacrolimus dosage and blood concentration and can be managed by dose reduction This is in contrast to CNI-induced chronic nephropathy, which is largely irreversible and can occur independently of acute renal dysfunction, CNI dosage, or blood concentration Studies have been conflicting on the protective effect of calcium channel blockers on the preservation of renal function for patients receiving CNIs In a multicenter, prospective, randomized, placebo-controlled study in 118 cadaveric renal transplant recipients receiving CSA, the use of a calcium channel blocker resulted in a significantly better allograft function at years and demonstrated an improvement in graft function, as assessed by serum creatinine and GFR, that was independent of lowered blood pressure.158 More research is being done with goals of improving the safety profile of CNIs and identifying safer alternatives Vancomycin The use of vancomycin hydrochloride has increased considerably, as it has become the standard therapy for treatment of methicillinresistant Staphylococcus aureus infections S aureus infection accounted for the largest proportion of healthcare-associated infections in pediatrics (central line–associated bloodstream infection, catheter-associated urinary tract infection, ventilator-associated pneumonia, and surgical site infection) with approximately one-third being methicillin-resistant S aureus.146 The synergistic nephrotoxicity of combination therapy involving vancomycin with piperacillintazobactam and aminoglycosides is well established, with a reported frequency of acute renal failure in the range of 20% to 30%.147,148 However, the nephrotoxicity of vancomycin alone increasingly is being recognized as high-dose therapy has become more common for the treatment of methicillin-resistant S aureus Vancomycin alone can cause renal injury in children without preexisting disease.149 In addition, pediatric administration of vancomycin plus piperacillin-tazobactam leads to higher rates of AKI.150 Vancomycin is excreted by glomerular filtration, 80% to 90% in an unaltered form.151 It is hard to determine the exact rates of vancomycin-related toxicity because most reported cases have had additional risk factors for acute renal failure, which makes it difficult to determine the true risk of treatment The mechanism by which it exerts its nephrotoxicity is unknown but is partially attributable to an increased production of reactive oxygen species and oxidative stress.152 Independent risk factors for nephrotoxicity include the use of concomitant nephrotoxic agents, age, duration of therapy, and drug levels achieved Trough levels higher than 15 mg/mL are associated with increased risk of nephrotoxicity, and peak levels also have been associated with increased nephrotoxicity.153 The dosing of vancomycin requires careful consideration of renal function and estimated GFR Trough levels should be monitored frequently in patients with fluctuating renal function Nonsteroidal Antiinflammatory Drugs In most circumstances, NSAIDs not pose a significant risk to patients with normal renal function However, in situations in which renal perfusion is compromised (which is relatively common with critically ill patients), the inhibition of prostaglandin-induced vasodilation with the use of NSAIDs may further compromise renal blood flow and exacerbate ischemia The following factors put patients at high risk of NSAID-induced nephrotoxicity: preexisting renal dysfunction; severe cardiovascular or hepatic failure; systemic lupus erythematosus; or the concomitant use of other potentially nephrotoxic medications, such as AGs, ACE inhibitors, and angiotensin receptor blockers.159 The renal effects of NSAIDs seem to be dependent on the type, dose, and duration of treatment Clinical features of NSAIDinduced nephrotoxicity include oliguria and oliguric-induced AKI, hypokalemia, proteinuria, hypertension, and fever Avoidance of NSAIDs is the best preventive strategy, especially for patients at risk of renal insufficiency or patients taking other nephrotoxic drugs Calcineurin Inhibitors The introduction of CNIs for transplant recipients has led to dramatic improvement in both allograft and patient survival The clinical use of CNIs often is limited by their nephrotoxic effect (18%–42% estimated incidence, which can present as two distinct and well-characterized forms: acute and chronic nephrotoxicity) CNI-induced AKI may occur as early as a few weeks or months after initiation of therapy Although the exact mechanism of nephrotoxicity is not fully understood, several factors have been implicated in the Contrast-Induced Nephropathy Contrast-induced nephropathy (CIN) AKI is an important complication in the use of iodinated contrast media that accounts for an estimated 11% to 12% of hospital-acquired AKI.160 The occurrence of AKI as a result of contrast will continue to increase, as there is growing use of imaging and interventional procedures in pediatric intensive care patients.161 At the same time, many patients in intensive and critical care units have compromised renal function, representing the most important risk factor for contrast-induced AKI CHAPTER 74 Glomerulotubular Dysfunction and Acute Kidney Injury Three core elements are intertwined in the pathophysiology of CIN: (1) direct toxicity of iodinated contrast to nephrons, (2) microshowers of atheroemboli to the kidneys, and (3) contrastand atheroemboli-induced intrarenal vasoconstriction.162 Direct toxicity to nephrons with iodinated contrast has been demonstrated and seems to be related to the osmolality of the contrast.163 Hence, low-ionic or nonionic and low-osmolar or iso-osmolar contrast agents were shown to be less nephrotoxic in vitro Microshowers of cholesterol emboli are believed to occur in up to 50% of percutaneous interventions where a guiding catheter is passed through the aorta Most of these showers are clinically silent; however, in approximately 1% of high-risk cases, acute cholesterol emboli syndrome can develop, which is manifested by AKI, mesenteric ischemia, decreased microcirculation to the extremities, and, in some cases, embolic stroke.164 Finally, intrarenal vasoconstriction as a pathologic vascular response to contrast media, and perhaps an organ response to cholesterol emboli, is a final hypoxic/ischemic injury to the kidney.165 Hypoxia triggers activation of the renal sympathetic nervous system and results in a reduction in RBF, especially in the outer medulla There is disagreement about the direct vasoconstrictor or vasodilator effects in the kidney of contrast agents when given to animals It is likely that in completely normal human renal blood vessels, contrast agents provoke a vasodilation and an osmotic diuresis When there is vascular disease, endothelial dysfunction, and glomerular injury, however, contrast and the multifactorial insult of renal hypoxia provoke a vasoconstrictive response and, hence, partially mediate an ischemic injury.166 The most important predictor of CIN is underlying renal dysfunction The “remnant nephron” theory postulates that after sufficient chronic kidney damage has occurred, the remaining nephrons assume the remaining filtration load, require increased oxygen demands, and are more susceptible to ischemic and oxidative injury Serum creatinine usually rises within the first 48 hours, peaking on the second or third day, with a return to baseline after weeks Contrast media are removed by dialysis, but there is no clinical evidence that prophylactic dialysis reduces the risk of AKI, even when carried out within hour or simultaneously with administration Hemofiltration performed before and after contrast administration deserves further investigation given reports of reduced mortality and need for hemodialysis However, the high cost and need for prolonged ICU care will also limit the utility of this prophylactic approach.167 There are no currently approved pharmacologic agents that will prevent CIN AKI With iodinated contrast, the pharmacologic agents tested in small trials that deserve further evaluation include theophylline, statins, ascorbic acid, and prostaglandin E1.168 Although popular, N-acetylcysteine has not been consistently shown to be effective Nine published meta-analyses document significant heterogeneity between studies and pooled odds ratios for N-acetylcysteine approaching unity.169 Importantly, only in those trials in which N-acetylcysteine reduced serum creatinine below baseline values because of decreased skeletal muscle production did renal injury rates seem to be reduced Thus N-acetylcysteine seems to falsely lower creatinine and not fundamentally protect the kidney against injury However, a study suggested that the use of volume supplementation with sodium bicarbonate together with N-acetylcysteine was more effective than N-acetylcysteine alone in reducing the risk of CIN Fenoldopam, dopamine, calcium channel blockers, atrial natriuretic peptide, and l-arginine have not been shown to be effective in the prevention of contrast-induced AKI Furosemide, 921 mannitol, and an endothelin-receptor antagonist are potentially detrimental Acute Renal Failure After Stem Cell Transplantation One of the most frequent complications of bone marrow transplant is renal failure, with 5% to 15% of all bone marrow transplant patients developing AKI and 5% to 20% of the survivors developing chronic renal failure.170 Hematopoietic stem cell transplantation is a common procedure for the treatment of malignancies and some nonmalignant hematologic disorders The process of stem cell transfusion predisposes these patients to renal failure because of prior chemotherapy, irradiation, sepsis, and exposure to nephrotoxic agents Complicating outcomes are newer conditioning regimens that allow for reduced intensity and nonmyeloablative regimens, thereby allowing patients with significant comorbidities to undergo transplantation with reduced morbidity and mortality These have led to challenges in the ICU management of these patients, because they already have residual organ injury A study of 29 pediatric patients who required continuous RRT in the ICU showed an almost 100% mortality at months post-ICU admission due to transplantrelated illness This study demonstrated the management and ethical difficulties being posed by hematopoietic stem cell transplant patients becoming critically ill and requiring organ support at tertiary care centers In contrast with the improving survival rates following stem cell transplantation, there are greater numbers of children surviving and progressing to end-stage renal disease Some of these patients are being treated with renal transplantation.171 A better understanding of the underlying histopathologic changes in renal morphology would perhaps lead to a better control of the renal insults that occur during the process of stem cell transfusion Some histopathology-based studies have shown a variety of findings in patients post–stem cell transplantation, including features of tubulitis and peritubular vasculitis These studies also show that kidneys from adult patients who had grade III-IV graft-versus-host disease were more likely to have tubulitis and peritubular capillaritis.172 Other studies have shown membranous GN and thrombotic microangiopathy to be common histologic features post–stem cell transplantation.173 However, there remains a paucity of pediatric studies examining renal histopathology in patients posttransplantation (see also Chapter 93) Urinary Tract Obstruction Obstruction of urine flow may result in AKI, although unilateral obstruction rarely causes AKI unless there is a single kidney or disease in the other kidney Both unilateral and bilateral ureteral obstructions are accompanied by an initial increase in RBF caused by afferent arteriolar vasodilation Relaxation of the preglomerular capillary sphincter is mediated by the local release of vasodilatory prostaglandins.174 Administration of indomethacin, a cyclooxygenase inhibitor, results in a marked reduction in the GFR after a decrease in glomerular plasma flow and an increase in both afferent and efferent arteriolar resistances This indicates an important role of vasodilatory prostaglandins in the maintenance of the GFR If the obstruction persists, RBF progressively decreases as afferent arteriolar resistance increases because of the overriding action of angiotensin II and thromboxane This vasoconstriction may 922 S E C T I O N V I I Pediatric Critical Care: Renal actually protect the kidney from damage during the period of obstruction Intratubular pressure rises after ureteral obstruction; this pressure is translated to the glomerulus as increased pressure in the Bowman space The contribution of this increased force opposing filtration to the decrease in the GFR is probably inconsequential because the intratubular pressure rise is transient.175 In addition, the elevation in Bowman space pressure is negated by an increase in the glomerular capillary pressure that increases the GFR RBF is redistributed from the outer to the inner cortex, resulting in relative ischemia of the kidney medulla.175 Various clinical causes of urinary tract obstruction exist The most important factors determining recovery of kidney and tubular function are the degree and severity of the obstruction Treatment consists of decompression of the urinary collecting system by removal of the obstruction or by urinary diversion Relief of obstruction is accompanied by a marked diuresis resulting from increased RBF and abnormal tubular function The increase in urine volume is related to a concentrating defect caused by loss of the medullary gradient and unresponsiveness of the kidney tubule to vasopressin.176,177 Hydrogen ion and potassium secretion may also be impaired The result is a distal type of kidney tubular acidosis with hyperkalemia.178 Conclusions This chapter has reviewed the major factors that contribute to the development of AKI, both in its oliguric and nonoliguric forms Also indicated are the clinical settings in which AKI may occur In addition, treatment modalities have been discussed Clearly, the challenge in AKI is the development of novel therapeutic strategies that will more directly intervene in the disease process and that can have an impact on the cellular and metabolic mechanisms that contribute to kidney cell injury Certain current investigations have been discussed because they may lead to clinical trials in the future Included among these agents are calcium channel blockers, adenine nucleotides, thyroid hormone, and oxyradical scavengers because they may modulate the full expression of kidney cell injury Only with an understanding of the pathophysiologic mechanisms in AKI can these potential therapeutics be applied in a clinical setting to the care of pediatric patients Key References Barletta GM, Bunchman TE Acute renal failure in children and infants Curr Opin Crit Care 2004;10:499-504 Bellomo R, Ronco C, Kellum JA, et al Acute renal failure-definition, outcome measures, animal models, fluid therapy and informational technology needs: 2nd International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group Crit Care 2004;8: R204-R212 Cook KM, Gillon J, Grisso AG, et al Incidence of nephrotoxicity among pediatric patients receiving vancomycin with either piperacillin-tazobactam or cefepime: a cohort study J Pediatric Infect Dis Soc 2019; 8(3):221-227 Hobbs DJ, Barletta GM, Rajpal JS, et al Severe paediatric systemic lupus erythematosus nephritis-a single-centre experience Nephrol Dial Transplant 2010;25:457-463 Jennette JC, Falk RJ Diagnosis and management of glomerulonephritis and vasculitis presenting as acute kidney failure Med Clin North Am 1990;74:893 Legendre CM, Muus LP, Greenbaum LA, et al Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome N Engl J Med 2013;368(23):2169-2181 The full reference list for this chapter is available at ExpertConsult.com e1 References Bellomo R, Ronco C, Kellum JA, et al Acute renal failure-definition, outcome measures, animal models, fluid therapy and informational technology needs: 2nd International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group Crit Care 2004;8:R204-R212 Akcan-Arikan Zappitelli M, Loftis LL, et al Modified RIFLE criteria in critically ill children with acute kidney injury Kidney Int 2007;71:1028-1035 Plotz FB, Bouma AB, van Wijk JA, et al Pediatric acute kidney injury in the ICU: an independent evaluation of pRIFLE criteria Intensive Care Med 2008;34:1713-1717 Wasung MT, Chawla LS, Madero M Biomarkers of renal function, which and when? Clin Chim Acta 2015;438:350-357 Zaffanello M, Antonucci R, Cuzzolin L, et al Early diagnosis of acute kidney injury with urinary biomarkers in the newborn J Matern Fetal Neonatal Med 2009;22(suppl 3):62-66 Lisowska-Myjak B Serum urinary biomarkers of acute kidney injury Blood Purif 2010;29:357-365 Schlondorff D, Ardaillou R Prostaglandins and other arachidonic acid metabolites in the kidney Kidney Int 1986;29:108-19 Halliday HL, Hirata T, Brady JP Indomethacin therapy for large patent ductus arteriosus in the very low birth weight infant: results and complications Pediatrics 1979;64:154-159 Kon V, Yoshioka T, Fogo A, Ichikawa I Glomerular actions of endothelin in vivo J Clin Invest 1989;83:1762-1767 10 Ichikawa I, Pfeffer JM, Pfeffer MA, Hostetter TH, Brenner BM Role of angiotensin II in the altered renal function of congestive heart failure Circ Res 1984;55:669-675 11 Mujais SK, Fouad FM, Textor SC, et al Transient renal dysfunction during initial inhibition of converting enzyme in congestive heart failure Br Heart J 1984;52:63-71 12 Hall JE, Guyton AC, Jackson TE, Coleman TG, Lohmeier TE, Trippodo NC Control of glomerular filtration rate by renin-angiotensin system Am J Physiol 1977;233:F366-72 13 Sutton TA, Fisher CJ, Molitoris BA Microvascular endothelial injury and dysfunction during ischemic acute renal failure Kidney Int 2002;62:1539-1549 14 Bohle A, Mackensen-Haen S, von Gise H Significance of tubulointerstitial changes in the renal cortex for the excretory function and concentration ability of the kidney: a morphometric contribution Am J Nephrol 1987;7:421-433 15 Venkatachalam MA, Jones DB, Rennke HG, Sandstrom D, Patel Y Mechanism of proximal tubule brush border loss and regeneration following mild renal ischemia Lab Invest 1981;45:355-365 16 Brezis M, Rosen S Hypoxia of the renal medulla—its implications for disease N Engl J Med 1995;332:647-655 17 Epstein FH, Agmon Y, Brezis M Physiology of renal hypoxia Ann N Y Acad Sci 1994;718:72-81; discussion 81-82 18 Weinberg JM The cell biology of ischemic renal injury Kidney Int 1991;39:476-500 19 Messam CA, Pittman RN Asynchrony and commitment to die during apoptosis Exp Cell Res 1998;238:389-398 20 Borkan SC, Emami A, Schwartz JH Heat stress protein-associated cytoprotection of inner medullary collecting duct cells from rat kidney Am J Physiol 1993;265:F333-F341 21 Schaudies RP, Nonclercq D, Nelson L, et al Endogenous EGF as a potential renotrophic factor in ischemia-induced acute renal failure Am J Physiol 1993;265:F425-F434 22 Green DE, Fry M, Blondin GA Phospholipids as the molecular instruments of ion and solute transport in biological membranes Proc Natl Acad Sci U S A 1980;77:257-261 23 Schrier RW, Arnold PE, Van Putten VJ, Burke TJ Cellular calcium in ischemic acute renal failure: role of calcium entry blockers Kidney Int 1987;32:313-321 24 Bergin E, Levine JS, Koh JS, Lieberthal W Mouse proximal tubular cell-cell adhesion inhibits apoptosis by a cadherin-dependent mechanism Am J Physiol Renal Physiol 2000;278:F758-F768 25 Siegel NJ, Glazier WB, Chaudry IH, et al Enhanced recovery from acute renal failure by the postischemic infusin of adenine nucleotides and magnesium chloride in rats Kidney Int 1980;17:338-349 26 Oken DE Hemodynamic basis for human acute AKI (vasomotor nephropathy) Am J Med 1984;76:702 27 Brezis M, Rosen S, Silva P, et al Kidney ischemia: a new perspective Kidney Int 1984;26:375 28 Myers BD, Moran SM Hemodynamically mediated acute kidney failure N Engl J Med 1986;314:97 29 Rasmussen HH, Bels LS Acute kidney failure: multivariate analysis of causes and risk factors Am J Med 1982;73:211 30 Schwartz GJ, Munoz A, Schneider MF, et al New equations to estimate GFR in children with CKD J Am Soc Nephrol 2009;20:629-637 31 Schwartz GJ, Haycock GB, Edelmann CM, et al A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine Pediatrics 1976;58:259-263 32 Uchino S, Kellum JA, Bellomo R, et al Acute renal failure in critically ill patients: a multinational, multicenter study JAMA 2005;294: 813-818 33 Seri I Cardiovascular, renal, and endocrine actions of dopamine in neonates and children J Pediatr 1995;126:333 34 Kellum JA, et al Use of dopamine in acute renal failure: a metaanalysis Crit Care Med 2001;29:1526-1531 35 Pelayo JC, Fildes RD, Jose PA Age-dependent kidney effects of intrakidney dopamine infusion Am J Physiol 1984;247:R212 36 Karajala V, Mansour W, Kellum JA Diuretics in acute kidney injury Minerva Anestesiol 2009;75:251-257 37 Rigden SP, Dillon MJ, Kind PR, et al The beneficial effect of mannitol on postoperative kidney function in children undergoing cardiopulmonary bypass surgery Clin Nephrol 1984;21:148 38 Malis CD, Cheung JY, Leaf A, et al Effects of verapamil in models of ischemic acute AKI in the rat Am J Physiol 1983;245:F735 39 Wang J, Dunn MJ Platelet activating factor mediates endotoxininduced acute kidney insufficiency in rats Am J Physiol 1987;253: F1283 40 Wagner K, Albrecht S, Neumayer HH Prevention of delayed graft function in cadaveric kidney transplantation by a calcium antagonist: preliminary results of two prospective randomized trials Transplant Proc 1986;18:510 41 Hull RW, Hasbargen JA No clinical evidence for protective effects of calcium channel blockers against acute kidney failure N Engl J Med 1985;313:1477 42 Finn WF, Hak LJ, Grossman SH Protective effect of prostacyclin on post ischemic acute AKIin the rat Kidney Int 1987;32:479 43 Kaufman RP Jr, Anner H, Kobzik L, et al A high plasma prostaglandin to thromboxane ratio protects against kidney ischemia Surg Gynecol Obstet 1987;165:404 44 Koelz AM, Bertschin S, Hermle M, et al The angiotensin converting enzyme inhibitor enalapril in acute ischemic AKI in rats Experientia 1988;44:172 45 Sridharan M, Go RS, Willrich MAV Atypical hemolytic uremic syndrome: review of clinical presentation, diagnosis and management J Immunol Methods 2018;461:15-22 46 Gaudio KM, Stromski M, Thulin G, et al Postischemic hemodynamics and recovery of kidney adenosine triphosphate Am J Physiol 1986;251:F603 47 Zeidel ML Kidney actions of atrial natriuretic peptide In: Brenner BM, Stein JH, eds Contemporary Issues in Nephrology New York: Churchill Livingstone; 1989 48 Shaw SS, Weidmann P, Hodler J, et al Atrial natriuretic peptide protects against acute ischemic AKI in the rat J Clin Invest 1987; 80:1232 49 Boydstun I, Najjar S, Kashgarian M, et al Postischemic thyroxin stimulates kidney mitochondrial adenine nucleotide translocator activity Am J Physiol 1995;268:E651 50 Straub E Effects of L-thyroxine in acute renal failure Res Exp Med (Berl) 1976;168:(2):81-87 51 Epstein FH, Silva P, Spokes K, et al Prevention with glycine of acute AKI caused by cis-platinum Kidney Int 1990;37:480 e2 52 Barletta GM, Bunchman TE Acute renal failure in children and infants Curr Opin Crit Care 2004;10:499-504 53 Goldstein SL, Somers MJ, Baum MA, et al Pediatric patients with multi-organ dysfunction syndrome receiving continuous renal replacement therapy Kidney Int 2005;67:653-658 54 Fliser D, Schroter M, Neubeck M, Ritz E Coadministration of thiazides increases the efficacy of loop diuretics even in patients with advanced renal failure Kidney Int 1994;46:482-488 55 Better OS, Winaver J Acute kidney failure In: Arieff A, DeFronzo R, eds Fluid, Electrolyte, and Acid-Base Disorders New York: Churchill Livingstone; 1995 56 Moghal NE, Brocklebank JT, Meadow SR A review of acute renal failure in children: incidence, etiology and outcome Clin Nephrol 1998;49:91-95 57 Bunchman TE, McBryde KD, Mottes TE, et al Pediatric acute renal failure: outcome by modality and disease Pediatr Nephrol 2001;16: 1067-1071 58 Fakhouri F, Zuber J, Fremeaus-Bacchi V, et al Haemolytic uraemic syndrome Lancet 2017;390:1–14 59 Karmali MA, Petric M, Lim C, et al The association between idiopathic hemolytic uremic syndrome and infection by verotoxin-producing Escherichia coli J Infect Dis 1985;151:775 60 Dixon BP Atypical hemolytic uremic syndrome Pediatr Clin North Am 2018;65(3):509-525 61 Picard C, Burtey S, Bornet C, Curti C, Montana M, Vanelle P Pathophysiology and treatment of typical and atypical hemolytic uremic syndrome [in French] Pathol Biol (Paris) 2015;63(3): 136-143 62 Siegler RL Management of hemolytic-uremic syndrome J Pediatr 1988;112(6):1014-1020 63 Noris M, Mescia F, Remuzzi G STEC-HUS, atypical HUS and TTP are all diseases of complement activation Nat Rev Nephrol 2012;8(11):622-633 64 Ardissino G, Tel F, Possenti I, et al Early volume expansion and outcomes of hemolytic uremic syndrome Pediatrics 2016;137(1) 65 Cataland SR, Wu HM How I treat: the clinical differentiation and initial treatment of adult patients with atypical hemolytic uremic syndrome Blood 2014;123(16):2478-2484 66 Kielstein JT, Beutel G, Fleig S, et al Best supportive care and therapeutic plasma exchange with or without eculizumab in Shiga-toxinproducing E coli O104:H4 induced haemolytic-uraemic syndrome: an analysis of the German STEC-HUS registry Nephrol Dial Transplant 2012;27:3807-3815 67 Legendre CM, Muus LP, Greenbaum LA, et al Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome N Engl J Med 2013;368(23):2169-2181 68 Menne J, Nitschke M, Stingele R, et al Validation of treatment strategies for enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome: case-control study BMJ 2012;345: e4565 69 Mele C, Remuzzi G, Noris M Hemolytic uremic syndrome Semin Immunol 2014;36:399-420 70 Wenderfer SE, Ruth NM, Brunner HI Advances in the care of children with lupus nephritis Pediatr Res 2017;81(3):406-414 71 Jennette JC, Falk RJ Diagnosis and management of glomerulonephritis and vasculitis presenting as acute kidney failure Med Clin North Am 1990;74:893 72 Kambham N Postinfectious glomerulonephritis Adv Anat Pathol 2012;19(5):338-347 73 Rodriguez-Iturbe B Epidemic poststreptococcal glomerulonephritis Kidney Int 1984;25:129 74 Balasubramanian R, Marks SD Post-infectious glomerulonephritis Paediatr Int Child Health 2017;37(4):240-247 75 Balow JE, Austin HA Kidney disease in systemic lupus erythematosus Rheum Dis Clin North Am 1988;14:117 76 Hikari LD, Benseler SM, Tyrrell PN, et al Clinical and laboratory characteristics and long-term outcome of pediatric systemic lupus erythematosus: a longitudinal study J Pediatr 2008;152:550-556 77 Hobbs DJ, Barletta GM, Rajpal JS, et al Severe paediatric systemic lupus erythematosus nephritis-a single-centre experience Nephrol Dial Transplant 2010;25:457-463 78 McCluskey RT The value of kidney biopsy in lupus nephritis Arthritis Rheum 1982;25:867 79 Vachvanichsanong P, McNeil E Pediatric lupus nephritis: more options, more chances? Lupus 2013;22(6):545-553 80 Sinha R, Raut S Pediatric lupus nephritis: management update World J Nephrol 2014;3:16-23 81 Ginzler EM, Dooley MA, Aranow C, et al Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis N Engl J Med 2005;353:2219-2228 82 Johnson JP, Moore Jr J, Austin HA, et al Therapy of anti-glomerular basement antibody disease: analysis of prognostic significance of clinical pathologic and treatment factors Medicine (Baltimore) 1985;64:219 83 Ellis EN, Wood EG, Berry P Spectrum of disease associated with anti-neutrophil cytoplasmic autoantibodies in pediatric patients J Pediatr 1995;126:40 84 Jones RB, Furuta S, Tervaert JW, et al Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis: 2-year results of a randomised trial Ann Rheum Dis 2015;74(6):1178-1182 85 Stone JH, Merkel PA, Spiera R, et al Rituximab versus Cyclophosphamide for ANCA-associated vasculitis N Engl J Med 2010;363: 221-232 86 Sakarcan A, Timmons C, Seikaly MG Reversible idiopathic acute renal failure in children with primary nephrotic syndrome J Pediatr 1994;125:723 87 Clavé S, Rousset-Rouvière C, Daniel L, Tsimaratos M Acute tubulointerstitial nephritis in children and chronic kidney disease Arch Pediatr 2019;26(5):290-294 88 Ellis D, Fried WA, Yunis EJ, et al Acute interstitial nephritis in children: a report of 13 cases and review of the literature Pediatrics 1981;67:862 89 Hadjiphilippou S, Kon SP Cardiorenal syndrome: review of our current understanding J R Soc Med 2016;109(1):12-17 90 Kumar U, Wettersten N, Garimella PS Cardiorenal syndrome: pathophysiology Cardiol Clin 2019;37(3):251-265 91 Ronco C, McCullough P, Anker SD, et al Cardio-renal syndromes: report from the consensus conference of the acute dialysis quality initiative Eur Heart J 2010;31(6):703-711 92 Testani JM, Khera AV, St John Sutton MG, et al Effect of right ventricular function and venous congestion on cardiorenal interactions during the treatment of decompensated heart failure Am J Cardiol 2010;105(4):511-516 93 Praught ML Are small changes in serum creatinine an important risk factor? Curr Opin Nephrol Hypertens 2005;14:265-270 94 Hui-Stickle S, Brewer ED, Goldstein SL Pediatric ARF epidemiology at a tertiary care center from 1999 to 2001 Am J Kidney Dis 2005;45:96-101 95 Rubinstein J, Sanford D Treatment of cardiorenal syndrome Cardiol Clin 2019;37(3):267-273 96 Cooper DS, Kwiatkowski DM, Goldstein SL, Krawczeski CD Acute kidney injury and cardiorenal syndromes in pediatric cardiac intensive care Pediatr Crit Care Med 2016;17(8 suppl 1):S250-S256 97 Jefferies JL, Goldstein SL Cardiorenal syndrome: an emerging problem in pediatric critical care Pediatr Nephrol 2013;28(6):855-862 98 Pedersen KR, Hjortdal VE, Christensen S, et al Clinical outcome in children with acute renal failure treated with peritoneal dialysis after surgery for congenital heart disease Kidney Int Suppl 2008;(108) S81-S86 99 Gist KM, Kwiatkowski DM, Cooper DS Acute kidney injury in congenital heart disease Curr Opin Cardiol 2018;33(1):101-107 100 Yuan SM Acute kidney injury after pediatric cardiac surgery Pediatr Neonatol 2019;60(1):3-11 101 Zappitelli M, Bernier PL, Saczkowski RS, et al A small post-operative rise in serum creatinine predicts acute kidney injury in children undergoing cardiac surgery Kidney Int 2009;76(8):885-892 ... susceptible to ischemic and oxidative injury Serum creatinine usually rises within the first 48 hours, peaking on the second or third day, with a return to baseline after weeks Contrast media are removed... 100% mortality at months post-ICU admission due to transplantrelated illness This study demonstrated the management and ethical difficulties being posed by hematopoietic stem cell transplant patients... pressure rises after ureteral obstruction; this pressure is translated to the glomerulus as increased pressure in the Bowman space The contribution of this increased force opposing filtration to