Acute kidney injury in an adolescent: Answers

Pediatric Nephrology https://doi.org/10.1007/s00467-020-04648-7 CLINICAL QUIZ Acute kidney injury in an adolescent: Answers Hulya Nalcacioglu 1 & Demet Tekcan 1 & Bilge Can Meydan 2 & Ozan Ozkaya 3 Received: 22 May 2020 / Accepted: 3 June 2020 # IPNA 2020 Keywords Acute kidney injury . Thinner addiction . Toluene . Youth What is the differential diagnosis of the patient’s kidney injury? First, we excluded the chronic state of this patient by looking at his previous creatinine value and experienced an acute rise in the plasma creatinine so defined as acute kidney injury (AKI) [1]. The basic diagnostic approach to our patient with AKI was to assess whether the patient has prerenal, postrenal, or intrinsic AKI. Postrenal AKI is an immediately curable cause and was ruled out in our patient due to the absence of signs of obstruction on urinary system ultrasound. At the initial admission to the local hospital, he was considered as having prerenal AKI with volume depletion because of vomiting and diarrhea. His physical examination findings of hypotension and tachycardia supported the prerenal AKI. However, despite the volume repletion, his renal function worsened and he was admitted to our hospital. It is well-known that patients with hypovolemia are at risk of progression from prerenal azotemia to acute tubular necrosis (ATN) with prolonged renal hypoperfusion. Taken together, clinical and laboratory findings of our patient supported the probable cause of AKI in this patient was prerenal AKI with superimposed renal failure, secondary to ischemic acute tubular necrosis. Ischemic ATN is frequently reversible, but the glomerular filtration rate in our patient does not improve with This refers to the article that can be found at https://doi.org/10.1007/ s00467-020-04641-0. * Hulya Nalcacioglu [email protected] 1 Pediatric Nephrology Department, Faculty of Medicine, Ondokuz Mayis University, Kurupelit, Samsun, Turkey 2 Pathology Department, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey 3 Pediatric Nephrology Department, Faculty of Medicine, Istinye University, Istanbul, Turkey the restoration of intravascular volume with intravenous fluids. Our patient denied the usage of NSAID or another drug which could exacerbate renal insufficiency with hypovolemia. The differential causes of intrinsic AKI can be classified as glomerular, vascular, and tubulointerstitial in origin. Lack of significant proteinuria, hypoalbuminemia, the absence of hematuria or red blood cell casts in urine sediment, normal glomeruli on biopsy without immunofluorescent deposits, and normal complement results excluded glomerulonephritis in our patient. Considering the negative ANCA results and normal glomerulus appearance on renal biopsy, ANCAassociated glomerulonephritis was dismissed. Vascular etiology was unlikely in the setting of normal blood cell count, normal complement levels, and the kidney biopsy without thrombotic microangiopathy. A viral nephritis was unlikely g i v e n th e n e g a t i v e v i r a l r e s u l t s an d a bs e n c e o f tubulointerstitial damage. The negative history for toxins was against the diagnosis of tubular injury. A renal biopsy was done due to the lack of apparent cause of AKI, and a rapid increase in serum creatinine levels. What does the renal biopsy reveal (Fig. 1a–b)? Light microscopy shows widespread severe acute tubular necrosis with fragmented red blood cell casts. Cytoplasmic sloughing, large nuclei with mitotic activity of degenerate flattened epithelium are prominent in the proximal tubule. There is no crystal, epithelial pigmentation, or inclusion. Glomeruli and vasculature are unremarkable with no epithelial or endocapillary proliferation, fibrinoid necrosis, and collapsing. Immunofluorescence staining was negative in the glomeruli and tubuli (not shown). Interstitial edema and mild inflammatory infiltrate with very few eosinophils is secondary to acute tubular injury. There is no widespread tubulointerstitial nephritis, granuloma-like histiocytic reaction. There is no tubulointerstitial atrophy and fibrosis. Renal biopsy findings of the patient were compatible with toxic acute tubular necrosis. Pediatr Nephrol Based on the clinical and renal biopsy findings, what could be the reason of AKI in this patient? Hypoxic/ischemic injury, drug-induced, exogenous toxins, endogenous toxins, and many causes listed in prerenal etiologies lead to intravascular volume depletion with structural tubular damage or ATN [1, 2]. In this report, the patient developed acute kidney injury within a few days following gastroenteritis. Renal biopsy showed ATN with tubular damage. Besides prednisone therapy, he required RRT to treat the complications of his ATN. Urine output and renal function improved and creatinine returned to normal in 2 weeks and prednisone was gradually discontinued. However, the etiology of AKI remained elusive. Although our patient denied exposure to any toxic substance, toxic etiology was suspected because of biopsy findings. On the day of discharge, from the hospital, upon closer questioning, his mother confessed that he had sniffed thinner with a group of friends for the first time. Although a rare event, it is unpredictable and can occur in first-time users. We were unable to analyze the chemical composition of the thinner mixture used by the patient. The patient is presently under the care of a psychiatrist for psychotherapy. The patient was seen in the clinic for follow-up 2 weeks after discharge; he looked healthy and had a blood pressure of 118/ 74 mmHg. Follow-up laboratory tests at that visit revealed a BUN of 7 mg/dL, creatinine of 0.7 mg/dL, Na of 142 mmol/l, K of 4.6 mmol/l, Cl of 104 mmol/l, and normal blood gas levels. Discussion Our patient had no history of renal disease or any potential nephrotoxic agents, other than thinner sniffing. He was exposed for the first time to thinner as an experimenter and presented with gastrointestinal tract system effects followed by nephrotoxic injury. It is a rare finding for the first-time users. This case is proposed to emphasize and awareness of the dangerous effect of thinner sniffing. Thinner is the most commonly used form among volatile substance abuse, due to its low cost, easily obtainable, and quick effect. It is found in many products used in daily life, such as lighters, paints, cleaning solutions, and some pens. Toluene, xylene, and derivatives of benzene or halogenated hydrocarbons were present as major compounds of thinner [3, 4]. There is no quantitative analysis of our patient’s blood or urine; we cannot be sure which solvent or solvents were responsible for the AKI of this patient. Based on the literature, the most reported substance in terms of its effect on the kidney is toluene. Toluene is a major component of the thinner. It is highly lipid-soluble and well absorbed through the lungs into the bloodstream and distributed primarily to tissues with high lipid content such as the nervous system, liver, kidneys, and adipose tissue. The Occupational Safety and Health Administration has determined that toluene levels of 2000 parts per million (ppm) are considered dangerous to life and health while the accepted upper limit for industrial exposure to toluene is 150 ppm [5]. It is metabolized mainly in liver by the cytochrome P450 system and excreted from the body by urine as hippuric acid. Urinary concentrations of hippuric acid higher than 2.5 g per g of creatinine is considered exposure [6]. The clinical toxicities due to the thinner are either from acute intoxication which is most often affected by the cardiac and neurological system at first or organ system dysfunction including the brain, heart, lung, kidney, liver, and bone marrow as a result of chronic abuse [7–17]. The mechanisms which are responsible for the organ damage with inhalant abuse depends upon a variety of factors including the concentration in inspired air, the blood/tissue partition coefficients, pulmonary blood flow, and the distribution of body fat [3, 4, 6]. Our patient presented as a case of acute thinner intoxication that presented with diarrhea and vomiting progressed to AKI. Inhalant abusers may develop nonspecific gastrointestinal symptoms such as nausea, vomiting, diarrhea, abdominal cramps, or loss of appetite. Transient hepatic damage and hepatorenal failure are other gastrointestinal consequences that have been reported in inhalant abusers [16, 17]. A review of literature reported several of renal diseases associated with chronic toluene abuse include electrolyte-acid/base disturbances such as hypokalemia, distal renal tubular acidosis, hematuria-proteinuria, glomerulonephritis, Goodpasture’s syndrome, or urinary calculi [10–15]. Although previous studies mostly reported renal tubular damage due to chronic thinner usage, several cases stated the development of glomerular and tubular renal damage in acute toluene poisoning as well [14, 18, 19]. Yurtseven et al. [18] described a 16-year-old boy who was addicted to toluene inhaling developed severe acute renal/ hepatic damage. He was treated with continuous hemodiafiltration and plasma exchange to eliminate hippuric acid and 10 days later; renal/hepatic functions were normal. Another case of reversible hepatorenal insufficiency has been reported in a 19-year-old patient who smelled toluene-based adherents for 3 years [19]. Hypokalemia and severe metabolic acidosis associated with toluene intoxication are well-known prominent findings and reported in the largest series with 22 patients by Cámara-Lemarroy et al. [14]. The histopathological changes of thinner inhalation were examined on rat kidneys for 6 weeks and tubular damage, severe tubulointerstitial nephritis were observed [20]. In our case, there were findings of detectable damage in the epithelium of proximal tubules parallel to the experimental results and reported cases. Our case showed reversible renal damage that presents itself as AKI. We believe that the determination of thinner exposure as an etiology of AKI in our patient have increased the Pediatr Nephrol awareness of both patient and his family in terms of avoiding from chronic thinner usage. The diagnosis of solvent use is difficult due to the absence of a specific laboratory test confirming solvent inhalation. A comprehensive history and a high index of suspicion, such as behavioral changes and characteristics of odor on breath or clothing are useful tips for detecting cases. Laboratory analysis of blood and urine samples collected up to 24 h after exposure may help in diagnosing the abuse of volatiles, although in some cases only a poor correlation has been established between blood toluene levels and clinical characteristics of toxicity as a result of rapid initial tissue distribution and elimination [3, 4, 21]. 5. 6. 7. 8. 9. 10. 11. 12. Conclusion In conclusion, the occurrence of AKI in our patient after thinner sniffing for only one time indicates a need for educating parents and young people about the potential threat of this volatile substance abuse. In view of the clinical presentation of our patient toluene exposure should be considered in the differential diagnosis in any young patient who presents with unexplained renal disorder. Compliance with ethical standards Conflict of interest The authors declare that they have no conflict of interest. References 1. 2. 3. 4. Khwaja A (2012) KDIGO clinical practice guidelines for acute kidney injury. 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