Renal tubular dysfunction in patients with American cutaneous leishmaniasis

Oliveira, Rosilene Aparecida de; Diniz, Lucyo Flávio Bezerra; Teotônio, Leonardo O.; Lima, Clara Taína Silva; Mota, Rosa Maria Salani; Martins, Alice Maria Costa; Sanches, Talita Rojas; Seguro, Antônio Carlos; Andrade, Lúcia; Silva, Geraldo Bezerra da; Libório, Alexandre Braga; Daher, Elizabeth De Francesco

doi:10.1038/ki.2011.251

Cited by 31 publications

(32 citation statements)

References 37 publications

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“…After treatment, six patients had persistent deficit (considering the inability to reduce urinary pH 5.5) similar to the approach used in our study. 14 In this study, the urinary MCP-1 and MDA levels were significant elevated compared with the control group. This study is the first study showing an increase in MCP-1 and MDA in VL.…”

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confidence: 66%

Preliminary Study on Tubuloglomerular Dysfunction and Evidence of Renal Inflammation in Patients with Visceral Leishmaniasis

Oliveira

Silva

Sampaio

et al. 2014

The American Journal of Tropical Medicine and Hygiene

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Visceral leishmaniasis (VL) is a re-emerging zoonosis of worldwide distribution. Monocyte chemotactic protein-1 (MCP-1) and malondialdehyde (MDA) are inflammation biomarkers that have never been investigated in VL. The aim of this study is to investigate the association between renal abnormalities and inflammation biomarkers in VL. This study is a preliminary prospective study with 16 VL adult patients evaluated before treatment compared with a group of 13 healthy volunteers and 5 VL patients evaluated after treatment. Urinary concentration and acidification tests were performed. MCP-1 and MDA were quantified in urine. Urinary concentration deficit was found in all VL patients before (100%) and four VL patients after (80%) treatment. Urinary acidification deficit was found in nine cases before (56.2%) and two cases after (40%) treatment. Urinary MCP-1 (374 ± 359 versus 42 ± 29 pg/mg creatinine, P = 0.002) as well as urinary MDA (5.4 ± 2.6 versus 2.0 ± 0.8 μmol/mL) showed significant differences between VL patients and controls. These data show that VL patients present urinary concentration and acidification deficit, which can persist even after specific treatment. Urinary MCP-1 and MDA are elevated in patients with VL, which suggests renal inflammation and incipient renal damage.

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confidence: 66%

Preliminary Study on Tubuloglomerular Dysfunction and Evidence of Renal Inflammation in Patients with Visceral Leishmaniasis

Oliveira

Silva

Sampaio

et al. 2014

The American Journal of Tropical Medicine and Hygiene

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“…To the best of our knowledge there are no published studies that explore the relationship between a protein change in a kidney cell and the exosome derived from that cell population but there are studies that demonstrate differences in urinary exosome proteins with kidney disease. Fetuin‐A is up‐regulated in cisplatin‐induced acute kidney injury (AKI) (Zhou et al 2006 a ), transcription factors increase in abundance following AKI and podocyte injury (Zhou et al 2008), whereas aquaporin 1 is decreased following ischaemia–reperfusion kidney injury (Sonoda et al 2009) and AQP2 is decreased in patients with American cutaneous leishmaniasis (Oliveira et al 2011). As the mCCDC11 cell line up‐regulates AQP2 in response to stimulation and AQP2 is an archetypal exosomal protein (Pisitkun et al 2004; Gaeggeler et al 2011), we measured cellular and exosomal AQP2 before and after stimulation with the synthetic vasopressin analogue desmopressin.…”

Section: Discussionmentioning

confidence: 99%

Exosomal transmission of functional aquaporin 2 in kidney cortical collecting duct cells

Street

Birkhoff

Menzies

et al. 2011

The Journal of Physiology

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Non-technical summary Like most cells, those of the kidney release protein and RNA in structures called exosomes. It is possible that the contents of exosomes released into the urine from one part of the kidney can alter the function of downstream cells. We have used a cell model to test whether exosomes act as cell-to-cell messengers within the kidney. First, cells were exposed to a hormone that regulates the body's retention of water. This increased the levels of water channels within the cells and also within their exosomes. Next, these exosomes were placed onto a separate batch of cells, which responded by increasing their transport of water. This study shows that exosomes are a new mechanism for the transfer of physiological information within the kidney.Abstract Exosomes are vesicles released following fusion of endosomes with the plasma membrane. Urine contains exosomes that are released from the entire length of the nephron and change in composition with kidney disease. Exosomes can shuttle information between non-renal cells via transfer of protein and RNA. In this study murine kidney collecting duct (mCCDC11) cells were used to demonstrate that exosomes can act as a signalling mechanism between cells. First, the release of exosomes by mCCDC11 cells was confirmed by multiple approaches. Following isopynic centrifugation, exosomal proteins flotillin-1 and TSG101 were identified in fractions consistent with exosomes. Electron microscopy demonstrated structures consistent in size and shape with exosomes. Exposure of mCCDC11 cells to the synthetic vasopressin analogue, desmopressin, did not affect exosomal flotillin-1 or TSG101 but increased aquaporin 2 (AQP2) in a doseand time-dependent manner that was highly correlated with cellular AQP2 (exosomal AQP2 vs. cellular AQP2, Pearson correlation coefficient r = 0.93). To test whether the ratio of exosomal AQP2/flotillin-1 is under physiological control in vivo, rats were treated with desmopressin. The ratio of AQP2/flotillin-1 in the urinary exosome was significantly increased. Inter-cellular signalling by exosomes was demonstrated: exosomes from desmopressin-treated cells stimulated both AQP2 expression and water transport in untreated mCCDc11 cells (water flow across cells: control exosome treatment 52.8 ± 11 μl cm −2 ; AQP2-containing exosomes 77.4 ± 4 μl cm −2 , P = 0.05, n = 4). In summary, the amount of AQP2 in exosomes released from collecting duct cells is physiologically regulated and exosomal AQP2 closely reflects cellular expression. Exosomes can transfer functional AQP2 between cells and this represents a novel physiological mechanism for cell-to-cell communication within the kidney. Abbreviations AQP2, aquaporin 2; AKI, acute kidney injury; mCCDC11, murine cortical collecting duct cell line; miRNA, microRNA; TEM, transmission electron microscopy; TSG101, tumor susceptibility gene 101.

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“…Our group has demonstrated that urinary exosomal AQP1 is decreased in a similar model (34). More recently, Oliviera et al (24) reported that urinary exosomal AQP2 might be a potential biomarker for the urinary concentration defect in patients with American cutaneous leishmaniasis. These findings indicate that examination of urinary exosomes could lead to the discovery of new noninvasive biomarkers of kidney disease.…”

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confidence: 93%

Excretion of urinary exosomal AQP2 in rats is regulated by vasopressin and urinary pH

Higashijima

Sonoda

Takahashi

et al. 2013

American Journal of Physiology-Renal Physiology

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Urinary exosomes are small vesicles secreted into urine from all renal epithelial cell types and known to contain proteins that are involved in renal secretion and reabsorption. Among these proteins, urinary exosomal aquaporin-2 (AQP2) has been suggested to be useful for diagnosis of renal disease. However, the mechanisms underlying the excretion of urinary exosomal AQP2 are largely unknown. In this study, we examined the mechanisms of urinary exosomal AQP2 excretion in vivo, using diuretics including furosemide (FS), an inhibitor of the sodium-potassium-chloride symporter; acetazolamide (ACTZ), an inhibitor of carbonic anhydrase; OPC-31260 (OPC), a vasopressin type 2 receptor antagonist; and NaHCO3, a urinary alkalizing agent. Samples of urine from rats were collected for 2 h just after treatment with each diuretic, and urinary exosomes were isolated by ultracentrifugation. Urinary exosomal AQP2 excretion was dramatically increased by treatment with FS accompanied by urine acidification or with ACTZ accompanied by urine alkalization. Immunohistochemistry showed that apical localization of AQP2 was clearly evident and the plasma vasopressin level was increased after each treatment. Although treatment with OPC alone had no significant effect, coadministration of OPC completely inhibited the FS-induced and partially reduced the ACTZ-induced responses, respectively. Treatment with NaHCO3 increased the excretion of urinary exosomal AQP2 accompanied by urine alkalization. This increased response was partially inhibited by coadministration of OPC. These data suggest that an increased plasma level of vasopressin promoted the excretion of urinary exosomal AQP2 and that urine alkalinization also increased it independently of vasopressin.

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Renal tubular dysfunction in patients with American cutaneous leishmaniasis

Cited by 31 publications

References 37 publications

Preliminary Study on Tubuloglomerular Dysfunction and Evidence of Renal Inflammation in Patients with Visceral Leishmaniasis

Preliminary Study on Tubuloglomerular Dysfunction and Evidence of Renal Inflammation in Patients with Visceral Leishmaniasis

Exosomal transmission of functional aquaporin 2 in kidney cortical collecting duct cells

Excretion of urinary exosomal AQP2 in rats is regulated by vasopressin and urinary pH

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