884 compared to high income countries (HIC) [5] Preventive measures are thus likely to be rela tively more effective in low income countries Since AKI is a heterogeneous syndrome, the primary mechanis[.]
M I McCulloch and A Bagga 884 compared to high-income countries (HIC) [5] Preventive measures are thus likely to be relatively more effective in low-income countries Since AKI is a heterogeneous syndrome, the primary mechanism resulting in renal injury is not the same for all causes Prerenal causes include dehydration, wherein serum creatinine rises due to a functional adaptive drop in the glomerular filtration rate (GFR) and is fluid responsive Differentiation between fluid responsive prerenal causes and other prerenal causes of acute tubular necrosis is important, since timely and appropriate fluid administration can help in reducing further renal injury The causes and presentation of AKI in LLMIC differ from that seen in HIC. The epidemiology is not well understood due to late presentation to hospitals, under-reporting, and reduced capacity to provide intensive care to severely ill patients AKI complicates 1–5% of patients with malaria, 20–85% with leptospirosis, and ~2% of patients with dengue hemorrhagic fever and dengue shock syndrome Hemorrhagic fever associated with hanta virus and AKI are common in parts of Asia and Latin America Two reports from India suggest that the incidence of AKI was 5–9% in inpatient wards and 25–36% in intensive care units The pattern of hospital-acquired AKI in tertiary hospitals in low-income countries is similar to that in high-income countries In rural or deprived areas with unsatisfactory health infrastructures, AKI is usually a community- acquired disease, affecting young and previously healthy individuals The chief causes of AKI in the developing world are diarrhea, septicemia, and endemic infections such as malaria, leptospirosis, and rickettsial infections HUS is an important cause of renal failure that often requires renal replacement therapy Appropriate use of antibiotics for skin and throat infections has led to a decline in AKI due to post- infectious glomerulonephritis Other causes include postsurgical complications, snake bites, and intake of traditional and nephrotoxic medicines Patients with HIV/AIDS may develop AKI in association with infections, hypovolemia, and use of nephrotoxic antiretroviral drugs Drug- induced hemolysis can occur with deficiency of glucose-6-phosphate dehydrogenase, frequently seen (15–20%) in north-west India, eastern Africa, and Nigeria Epidemics of AKI can occur after disasters, e.g., earthquakes or hurricanes, and are largely attributed to rhabdomyolysis resulting in crush syndrome Venomous snake bites account for a proportion of patients with AKI in India, Burma, and Thailand Exposure to industrial chemicals, including copper sulfate, might cause AKI in the tropics Traditional remedies from plant toxins and indigenous delicacies, e.g., djenkol beans and mushrooms, may lead to AKI in Africa and Southeast Asia Renal stones are an important cause of obstructive uropathy in northeast Africa and western Asia Shiga toxin-associated HUS, due to gastrointestinal infection with enterohemorrhagic E coli (EHEC) or Shigella dysenteriae, is the predominant cause of AKI in the developed world and in many developing countries Improved hygiene and appropriate use of antibiotics has resulted in a declining, and almost absent transmission of S dysenteriae in India Tertiary care centers in India therefore encounter more patients with atypical HUS than Shiga toxin-associated disease Infection was the most common cause of pediatric AKI in a tertiary hospital in south India during 2010–11; non-communicable diseases and drug use were also notable In Nigeria, primary kidney disease (39%; mostly acute glomerulonephritis and nephrotic syndrome), sepsis (26%), and malaria (11%) were chief causes of AKI. Accidental contamination of medications can lead to epidemics of pediatric deaths from AKI, such as occurred with diethylene glycol contamination of agents prescribed for cough and fever in Haiti, Bangladesh, and India iagnostic Evaluation (See Also D Chaps 43 and 44) Clinical Evaluation In patients with oliguria, the history should include questions on prerenal causes: vomiting, diarrhea, blood and volume loss, and fluid intake 45 Acute Kidney Injury in Less Well-Resourced Countries in the last 24-hours Acute tubular necrosis is the chief cause of AKI in hospitalized children and occurs in multiple settings: sepsis with capillary leak, burns, cardiac dysfunction, and inadequate fluid replacement Attention is given to fluid balance; negative balance suggests dehydration, and progressive increase in weight indicates fluid accumulation History is obtained for features of the underlying cause: edema, hematuria, hypertension (glomerulonephritis); dysentery, pallor, thrombocytopenia (hemolytic uremic syndrome); sudden pallor, jaundice, cola-colored urine (intravascular hemolysis); rash, arthritis (SLE, vasculitis); abdominal colic, hematuria, dysuria (nephrolithiasis); and interrupted urinary stream, palpable urinary bladder (obstruction of lower urinary tract) Urine output is often preserved in patients with AKI secondary to nephrotoxic medications and radiocontrast agents Anuria may be seen in patients with urinary tract obstruction, cortical necrosis, bilateral vascular occlusion, and severe glomerulonephritis Polyuria is seen in patients with partial ureteral obstruction and AKI with pre-existing tubular disorders The diagnosis of AKI depends on serial monitoring of serum creatinine Although efforts have been made to identify biomarkers that detect injury of renal tissue, including neutrophil gelatinase- associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18, these so far have limited roles in the diagnosis of AKI Laboratory Evaluation Investigations to confirm the etiology of AKI, assess severity, and detect complications are routinely performed Prerenal conditions should be distinguished from intrinsic causes In established acute tubular necrosis, diminished tubular function results in high urine sodium (>40 mEq/L) and dilute urine (10–15% is shown to be associated with an increased risk of mortality Fluid management should be meticulous in order to mitigate this complication Daily fluid intake should be restricted to insensible losses (400 ml/m2 body surface area) and ongoing renal and gastrointestinal losses Insensible losses are replaced intravenously with 10% dextrose, while urine and extrarenal losses are replaced with 0.45% saline in 5% dextrose The oral route for fluid therapy is preferred, since it enables delivery of oral nutrition In fluid overloaded patients, less than the total urine output should be replaced to promote negative balance The daily fluid prescription should be guided by strict input and output monitoring, daily weight, physical examination, and serum sodium Judicious fluid administration with appropriate fluid composition should allow 0.5–1% weight loss per day in fluid overloaded patients Low serum sodium, hypertension, and failure to lose weight suggest excessive fluid intake, while weight loss and increasing sodium concentration suggest inadequate free water replacement Patients with oligo-anuria are at risk of hyperkalemia; potassium-containing fluids should be avoided Sodium intake should be restricted to 2–3 mEq/kg/day to avoid hypernatremia and fluid retention In the setting of non-oliguric AKI, patients may lose excessive fluid and electrolytes and need potassium and sodium supplements Patients with prolonged duration of AKI may develop hyperphosphatemia, which is managed with dietary phosphate restriction and oral phosphate binders Pharmacologic Therapy There are limited data on the efficacy of pharmacologic agents for therapy of AKI. While dopamine in low doses improves renal blood flow and sodium excretion, this effect is short lasting and quite variable There is no evidence that use of low-dose dopamine or fenoldopam prevents or improves renal recovery in AKI. Intravenous 45 Acute Kidney Injury in Less Well-Resourced Countries furosemide may increase urine output in some patients, but there is no evidence that it improves renal recovery or long-term prognosis of patients with AKI. A single dose of theophylline (5–8 mg/ kg/day) has been shown to reduce the incidence of severe AKI in term neonates with severe birth asphyxia [7] Nutrition Patients with AKI are critically ill, have increased metabolic requirements, and show protein catabolism Adequate nutritional supplementation is a crucial component of AKI management Protein intake should be 0.8–1.2 g/kg/day, which may be increased to 1.0–1.5 g/kg/day in patients on peritoneal or hemodialysis Patients should receive 60–70 Cal/kg/day, which is 20–30% above the basal needs Enteral feeding is preferred for patients with AKI. Patients on dialysis require supplementation of water-soluble vitamins and micronutrients [8, 9] Fluid Administration In LLMIC, the majority of cases of AKI are due to malaria, diarrhea, snake bites, and sepsis Treatment includes the administration of intravenous fluids, which has become controversial There is no clear consensus on the following questions: • • • • • Which fluid? How much? Over what time period? Intravenous or oral? What percentage fluid overload is acceptable – 10% or 20%? [10] Fluid Boluses The role of fluid boluses in the management of acute AKI is controversial One study which sparked this discussion was the FEAST trial [11] which was conducted in East Africa looking at 887 bolus fluids in septic children Poorer outcomes were seen in those receiving boluses Subsequent publications have sought to explain this observation without coming to a clear conclusion [12], but the FEAST trial has raised awareness that too much intravenous fluid given too rapidly in sick children can be deleterious As a result, the World Health Organization (WHO) and numerous international pediatric bodies (e.g., American Academy of Pediatrics) have advised caution when administering intravenous fluid rapidly or in large volumes without intermittent clinical assessment Sepsis and septic shock are frequently associated with AKI. Studies of early goal-directed therapies (EGDT) for septic shock in adults have not been as promising as originally thought; there have been no large trials of EGDT in pediatrics [13] One meta-analysis confirmed that EGDT as a packaged protocol of care was not superior to usual care, with questions remaining regarding the most effective fluid and vasopressor regimens, the role of hemodynamic monitoring including central venous pressure measurement and appropriate targets in the resuscitation of patients with sepsis and septic shock The future of sepsis therapy may lie with a more individualized approach with understanding of the complex interplay among host genetics, individual pathophysiological features, and the infective agent Another hypothesis that AKI is due to renal microcirculatory alterations is currently being studied using the sublingual microcirculation as a surrogate for the renal microcirculation [14] In children in LLMIC, many intensive care therapies such as central lines and vasopressors may not be easily available or even affordable and thus the emphasis remains on fluid therapy The predominant use of 0.9% saline in the management of AKI has been questioned This is a challenge in LLMIC as 0.9% saline is inexpensive and easily available An alternative for intravenous fluid use, Ringer’s lactate, is now being used in many centers with the lactated base being helpful in treating acidosis Individuals may be concerned about the potassium content of 4 mmol/l in this fluid, but this does not usually result in adverse events M I McCulloch and A Bagga 888 Fluid Overload Studies in well-resourced countries have shown that fluid overload in a pediatric intensive care setting has a higher incidence of renal replacement therapy requirement (in the form of continuous renal replacement therapy (CRRT)), as well as higher morbidity and mortality [10, 15] The degree of fluid overload (%FO) at CRRT initiation can be calculated using the following formula [16] %FO = (Fluid In ‐ Fluid Out)/(PICU admission weight) × 100% Stuart Goldstein and colleagues’ work with the Prospective Pediatric CRRT Registry [16] demonstrated that fluid overload of >20% over admission weight was associated with poorer outcomes and the need for CRRT. This is very relevant in LLMIC as this is a relatively easy measurement The above formula requires only admission weights and calculations of “fluid in and out” without any sophisticated technology Establishing this admission weight baseline with regular fluid monitoring has become accepted practice even in resource-poor settings, and will reduce the risk of excessive fluid resuscitation progressing to fluid overload requiring removal by dialysis/hemofiltration which may not be available (Fig. 45.1) [6] Drugs to Remove Fluid Managing a child who is passing at least some urine is easier than managing an anuric patient, especially in areas where dialysis is not available Fluid Balance R E S U C I T A T I O N Maintenance/ Homeostasis Removal/ Recovery Time Fig 45.1 The acute kidney injury fluid epidemiology paradigm and a proposed fluid accumulation 3-phase conceptual model for the patient with acute kidney injury (Reprinted with permission from Goldstein [6] SAGE Publications) Furosemide is a controversial drug for use in the oliguric or anuric AKI patient raising concerns for the increased work of the kidney as well as the potential of ototoxicity Furosemide, however, is an inexpensive drug that is easily available in most LLMIC where it is used either as 1 mg/kg/dose boluses 6–8-hourly or even as an infusion (0.1–1 mg/kg/h iv infusion) Aminophylline has been used intermittently in the past, mainly in neonatology as a supplementary diuretic,[7], and there is some new work suggesting that the use of a combination of furosemide and aminophylline (1 mg/kg/dose hourly iv infusion) works well to produce a diuresis This could be trialed in a patient before switching to CRRT in resource-limited cases Drug Administration Many drugs, both conventional and alternative preparations, have the potential to cause or contribute to AKI. Common and easily available drugs which are implicated in AKI include non- steroidal anti-inflammatory drugs (NSAIDs) such as Ibuprofen for the treatment of fever or pain in children This is often given in the face of poor feeding, malnutrition, and dehydration resulting in a second “hit” to kidneys which may already be vulnerable Aminoglycosides are also implicated in AKI and are both cheap and easily available, resulting in use as first-line therapy for sepsis These drugs are often given without monitoring drug levels as drug levels may not be available on the whole or just too costly to routinely Radiocontrast used in investigations such as CT scans or cardiac catheterization is also implicated in drug-related AKI and may in some cases be prevented by pre-hydration, which is achievable in less well-resourced areas In severely ill patients, inotropes may also be added Recent studies have shown that the use of Dopamine in sepsis can be associated with an increase in mortality compared to Adrenaline (epinephrine) [17] This is thought to be due to Dopamine impairment of the cellular immune function during sepsis These drugs are often 45 Acute Kidney Injury in Less Well-Resourced Countries used to support blood pressure in septic patients to improve renal perfusion which is decreased in AKI Adrenaline (epinephrine) is a cheap and easily available drug which can be used as a dilute peripheral infusion (in situations where ICU and central venous access are not available) and has value in sepsis where fluid boluses have failed to improve perfusion (starting Adrenaline infusion at 0.02 mcg/kg/min) Traditional medications which come in many forms have also been responsible for AKI in many situations These drugs are often produced with local substances, the identity of which may not be known, as well as the side effects thereof Sclerosant agents can result in both poor feeding if given orally or severe diarrhea and bowel necrosis if given rectally Family education should be given to prevent this and should be happening at the community level Clean water security is probably one of the most important ways of preventing AKI, and the use of chlorine tablets or boiling and filtering water is essential to teach even at school level New ideas such as the use of used dialyzers in a membrane filtration device have been implemented in Ghana – Easy Water for Everyone (https://www.easywaterforeveryone.org) This simple strategy has the potential for preventing AKI from diarrheal disease in less well- resourced communities Snake and insect bites are also responsible for AKI in many regions In Africa, malaria is responsible for much AKI morbidity and is one of the most frequent causes of mortality This can be prevented to some extent by insecticide spraying and mosquito nets Work on a malaria vaccine is at a fairly advanced stage and is eagerly awaited enal Replacement Therapy (RRT): R Table 45.1 In situations where conservative management of AKI has failed, early initiation of RRT may prevent complications and reduce mortality [18] Advances in the use of RRT in pediatrics have led 889 to a higher standard of care for young and critically ill patients The type of RRT chosen for treatment of both AKI as well as end-stage kidney disease (ESKD) depends on the availability of RRT in that region In HIC, decisions as to what kind of dialysis is used depend on patient size as well as clinicians’ and parental choice In LLMIC, this decision is severely restricted by availability of forms of RRT. This can range from no access at all to any form of dialysis for children; in some LLMIC settings the only available option is chronic hemodialysis (HD) in an adult unit using adult-sized machines and consumables which is only possible for teenagers and larger children Peritoneal dialysis (PD), both acute and chronic, is accepted as most appropriate for most children and infants An international dialysis survey showed PD to be available in almost all acute settings surveyed [19] (Table 45.2) Unfortunately, information from Africa, South America, and some parts of Asia was not available Commercial PD fluid which is dextrose- based is available as a lactate-based buffer or a more biocompatible bicarbonate buffer which is more physiologic but comes at an increased cost There is a growing trend of reduced use of PD in chronic dialysis with the increased growth of HD units across the world International organizations such as the International Society of Nephrology (ISN) and International Society of Peritoneal Dialysis (ISPD) have tried to promote the concept of “PD First” to initiate chronic dialysis, with HD as a second choice This has been hampered by the lack of commercial PD fluids, availability of PD catheters, and surgeons comfortable with inserting PD catheters, especially in pediatric patients In the treatment of AKI, acute PD was available in 100% of pediatric intensive care units surveyed [19] The challenge in LLMIC is the availability of both fluids and catheters Saving Young Lives (SYL) is an organization which is a collaboration of the International Society of Nephrology (ISN), the International Pediatric Nephrology Association (IPNA), the International Society of Peritoneal Dialysis (ISPD), and EuroPD. This group has started as a ... treating acidosis Individuals may be concerned about the potassium content of 4 mmol/l in this fluid, but this does not usually result in adverse events M I McCulloch and A Bagga 888 Fluid Overload... over admission weight was associated with poorer outcomes and the need for CRRT. This is very relevant in LLMIC as this is a relatively easy measurement The above formula requires only admission... patient size as well as clinicians’ and parental choice In LLMIC, this decision is severely restricted by availability of forms of RRT. This can range from no access at all to any form of dialysis