Vitamin D deficiency is a potential risk factor for lipid Amphotericin B nephrotoxicity

Abstract

Invasive fungal infections (IFI) is a worldwide serious health problem and Amphotericin B (AmB) has been considered the drug of choice for IFI treatment. Despite its efficacy, clinical use of AmB has been associated with renal toxicity. Some lines of evidence have shown that an extemporaneous lipid emulsion preparation of AmB (AmB/LE) was able to attenuate nephrotoxicity, presenting similar benefits at a lower cost. Studies have been demonstrating that hypovitaminosis D may hasten the progression of kidney disease and reflect on a worse prognosis in cases of drug-induced nephrotoxicity. In view of the high worldwide incidence of hypovitaminosis D, the aim of this study was to investigate whether vitamin D deficiency may induce AmB/LE-related nephrotoxicity. Wistar rats were divided into four groups: control, received a standard diet for 34 days; AmB/LE, received a standard diet for 34 days and AmB/LE (5 mg/kg/day) intraperitoneally in the last 4 days; VDD, received a vitamin D-free diet for 34 days; and VDD+AmB/LE, received a vitamin D-free diet for 34 days and AmB/LE as described. At the end of the protocol, animals were euthanized and blood, urine and renal tissue samples were collected in order to evaluate AmB/LE effects on renal function and morphology. Association of AmB/LE and vitamin D deficiency led to diminished glomerular filtration rate and increased tubular injury, evidenced by reduced renal protein expression of NaPi-IIa and TRPM6 leading to hyperphosphaturia / hypermagnesuria. VDD+AmB/ LE rats also presented alterations in the PTH-Klotho-FGF-23 signaling axis, urinary concentrating defect and hypertension, probably due to an inappropriate activation of the reninangiotensin-aldosterone system. Hence, it is important to monitor vitamin D levels in AmB/ LE treated patients, since vitamin D deficiency induces AmB/LE nephrotoxicity.

The Blockade of TACE-Dependent EGF Receptor Activation by Losartan-Erlotinib Combination Attenuates Renal Fibrosis Formation in 5/6-Nephrectomized Rats Under Vitamin D Deficiency

“…In addition to the well-known risk factors related to the CKD progression, other studies have been highlighting the hypovitaminosis D as a non-traditional aggravating factor for renal diseases (4-8, 31, 32). Previously, we demonstrated that VDD not only impaired the recovery but also accelerated the renal disease progression, exerting an important role on the process of RFF in different experimental models (4)(5)(6)(7)(8)(9)31). Although most studies have been focusing their efforts on the mechanisms underlying RFF, there is a lack of effective anti-fibrotic therapies which could efficiently block or reverse the progression of CKD.…”

Prognóstico de pacientes cardiopatas com injuria renal aguda submetidos a tratamento dialítico

“…Em estudo sobre fatores de risco para IRA em UTI, observou-se que 7,5% dos pacientes apresentaram HAS (2,22) , IC, hipovolemia, uso de drogas vasoativas, como a noradrenalina, a dobutamina, a dopamina e o uso de antibióticos (2,11,24) . Concluiu-se que ter três ou mais fatores de risco associados aumentavam a possibilidade de desenvolvimento da doença (2) .…”

“…A utilização de drogas nefrotóxicas e a hipovolemia eram suas principais causas. Atualmente, outros fatores etiológicos contribuem para o seu desenvolvimento, incluindo eventos iatrogênicos, como a hipotensão arterial durante as cirurgias, diarreia intensa secundária à infecção fúngica, em especial por Clostridium difficile, uso de antibióticos nefrotóxicos (anfotericina B, aminoglicosídeos), anti-inflamatórios não esteroides (AINEs), infecções, sepse, uso de contrastes para procedimentos diagnósticos (como cinecoronarioangiografia, tomografias, ressonância magnética), afecções cardiovasculares (principalmente IC, IAM), idade avançada, sexo masculino, localização geográfica e condição socioeconômica, que inclusive modificam consideravelmente os dados epidemiológicos e eventos futuros da doença (11) .…”

Cathelicidin protects mice from Rhabdomyolysis-induced Acute Kidney Injury

“…Four-mm histological sections of renal tissue were stained with hematoxylin-eosin and examined under light microscope. For the evaluation of renal damage, 20-30 grid fields (x400 magnification) measuring 0.245 mm 2 were evaluated by graded scores, according to the following criteria: (0), less than 5% of the field showing tubular epithelial swelling, vacuolar degeneration, inflammatory infiltrate, necrosis and desquamation; (1), 5-25% of the field presenting renal lesions; (2), involvement of 25-50% with renal damage; (3), 50-75% of damaged area; (4), more than 75% of the grid field presenting renal lesions (n = 8 mice per group) [20].…”