Acute Kidney Injury (AKI) in Young Synthetic Cannabinoids Abusers.

Background. Synthetic cannabinoid-related acute kidney injury represents an increasingly important public health issue due to the diagnostic challenges given by low clinical suspicion of the disease and the frequent undetectability in routine drug tests. Methods. A systematic literature search on PubMed was carried out until 31 January 2022. Case reports, case series, retrospective and prospective studies, as well as reviews on acute kidney injury related to the consumption of synthetic cannabinoid were searched. Results. The systematic review process selected 21 studies for a total of 55 subjects with synthetic cannabinoid-induced acute kidney injury. Renal damage was demonstrated by elevated serum creatinine levels in 49 patients (89%). On renal ultrasound, the most frequent finding was an increase in cortical echogenicity. Renal biopsy, performed in 33% of cases, revealed acute tubular damage, acute tubulointerstitial nephritis, and acute interstitial nephritis, in decreasing order of frequency. Conclusion. Prompt identification and treatment of synthetic cannabinoid-related acute kidney injury represent a sensitive public health goal both for the acute management of damage from synthetic cannabinoids and for the prevention of chronic kidney disease.

Acute Kidney Injury Following Star Fruit Ingestion: A Case Series.

Star fruit (Averrhoa carambola) is a popular fruit in many tropical countries, including Sri Lanka. It is rich in oxalic acid, which is nephrotoxic in higher concentrations. The development of both acute (AKI) and chronic kidney injury after oxalate nephropathy is often underrecognized. Here we discuss the risk factors, clinical features, treatment, and outcomes of 4 patients who developed AKI after star fruit ingestion. Baseline clinical characteristics, the amount of star fruit ingested, clinical presentation, investigation, and outcome of the patients (ages 28, 50, 54, and 55 y; all male) were traced. More common symptoms of acute star fruit intoxication were nausea, vomiting, and abdominal and back pain, followed by low urine output and high serum creatinine over hours to days. Urinary analysis of all patients demonstrated oxalate crystals. Histopathologic examination of renal tissues of all 4 patients revealed acute tubular damage with calcium oxalate crystals, interstitial edema, and inflammatory cellular infiltration. The presence of calcium oxalate crystals was further confirmed with the brilliant birefringence seen under polarized light. Two patients needed intermittent hemodialysis over a week owing to oliguria and uremia. The other 2 patients did not require hemodialysis and had improvement of renal function with supportive treatment. All had high renal function on discharge but were back to normal within a month. This study highlights AKI as a serious complication of star fruit ingestion. The type and quantity of star fruit ingested and some patient factors may play a role in the pathogenesis of AKI. Public education about this serious uncommon complication is important.

Circulating FH Protects Kidneys From Tubular Injury During Systemic Hemolysis.

Intravascular hemolysis of any cause can induce acute kidney injury (AKI). Hemolysis-derived product heme activates the innate immune complement system and contributes to renal damage. Therefore, we explored the role of the master complement regulator Factor H (FH) in the kidney's resistance to hemolysis-mediated AKI. Acute systemic hemolysis was induced in mice lacking liver expression of FH (hepatoFH-/-, ~20% residual FH) and in WT controls, by phenylhydrazine injection. The impaired complement regulation in hepatoFH-/- mice resulted in a delayed but aggravated phenotype of hemolysis-related kidney injuries. Plasma urea as well as markers for tubular (NGAL, Kim-1) and vascular aggression peaked at day 1 in WT mice and normalized at day 2, while they increased more in hepatoFH-/- compared to the WT and still persisted at day 4. These were accompanied by exacerbated tubular dilatation and the appearance of tubular casts in the kidneys of hemolytic hepatoFH-/- mice. Complement activation in hemolytic mice occurred in the circulation and C3b/iC3b was deposited in glomeruli in both strains. Both genotypes presented with positive staining of FH in the glomeruli, but hepatoFH-/- mice had reduced staining in the tubular compartment. Despite the clear phenotype of tubular injury, no complement activation was detected in the tubulointerstitium of the phenylhydrazin-injected mice irrespective of the genotype. Nevertheless, phenylhydrazin triggered overexpression of C5aR1 in tubules, predominantly in hepatoFH-/- mice. Moreover, C5b-9 was deposited only in the glomeruli of the hemolytic hepatoFH-/- mice. Therefore, we hypothesize that C5a, generated in the glomeruli, could be filtered into the tubulointerstitium to activate C5aR1 expressed by tubular cells injured by hemolysis-derived products and will aggravate the tissue injury. Plasma-derived FH is critical for the tubular protection, since pre-treatment of the hemolytic hepatoFH-/- mice with purified FH attenuated the tubular injury. Worsening of acute tubular necrosis in the hepatoFH-/- mice was trigger-dependent, as it was also observed in LPS-induced septic AKI model but not in chemotherapy-induced AKI upon cisplatin injection. In conclusion, plasma FH plays a key role in protecting the kidneys, especially the tubules, against hemolysis-mediated injury. Thus, FH-based molecules might be explored as promising therapeutic agents in a context of AKI.

Markers of acute kidney injury in children undergoing hematopoietic stem cell transplantation.

Acute kidney injury (AKI), one of the major complications in children undergoing hematopoietic stem cell transplantation (HSCT), is an independent predictor of the patient's survival and a prognostic factor of progression to chronic kidney disease (CKD). Despite the multifaceted role of AKI, its early diagnosis in the course of HSCT remains a challenge. These difficulties may result from the inefficiency of traditional methods used to assess kidney function, like serum creatinine or estimated glomerular filtration rate. Moreover, the list of potential AKI markers tested in HSCT conditions is limited and does not involve indexes evaluated in the pediatric population. This review summarizes current knowledge on the pathophysiology of AKI developing in the course of HSCT; presents well-known markers of AKI that are potentially applicable in children who have undergone HSCT; discusses the role of new markers in diagnosing AKI and predicting the renal outcome in children undergoing HSCT; and analyzes the prospects for the use of new tools for assessing kidney injury in everyday clinical practice.

Direct acute tubular damage contributes to Shigatoxin-mediated kidney failure.

The pathogenesis and therapy of Shigatoxin 2 (Stx2)-mediated kidney failure remain controversial. Our aim was to test whether, during an infection with Stx2-producing E. coli (STEC), Stx2 exerts direct effects on renal tubular epithelium and thereby possibly contributes to acute renal failure. Mice represent a suitable model because they, like humans, express the Stx2-receptor Gb3 in the tubular epithelium but, in contrast to humans, not in glomerular endothelia, and are thus free of glomerular thrombotic microangiopathy (TMA). In wild-type mice, Stx2 caused acute tubular dysfunction with consequent electrolyte disturbance, which was most likely the cause of death. Tubule-specific depletion of Gb3 protected the mice from acute renal failure. In vitro, Stx2 induced secretion of proinflammatory cytokines and apoptosis in human tubular epithelial cells, thus implicating a direct effect of Stx2 on the tubular epithelium. To correlate these results to human disease, kidney biopsies and outcome were analysed in patients with Stx2-associated kidney failure (n = 11, aged 22-44 years). The majority of kidney biopsies showed different stages of an ongoing TMA; however, no glomerular complement activation could be demonstrated. All biopsies, including those without TMA, showed severe acute tubular damage. Due to these findings, patients were treated with supportive therapy without complement-inhibiting antibodies (eculizumab) or immunoadsorption. Despite the severity of the initial disease [creatinine 6.34 (1.31-17.60) mg/dl, lactate dehydrogenase 1944 (753-2792) U/l, platelets 33 (19-124)/nl and haemoglobin 6.2 (5.2-7.8) g/dl; median (range)], all patients were discharged after 33 (range 19-43) days with no neurological symptoms and no dialysis requirement [creatinine 1.39 (range 0.84-2.86) mg/dl]. The creatinine decreased further to 0.90 (range 0.66-1.27) mg/dl after 24 months. Based on these data, one may surmise that acute tubular damage represents a separate pathophysiological mechanism, importantly contributing to Stx2-mediated acute kidney failure. Specifically in young adults, an excellent outcome can be achieved by supportive therapy only.