2D), suggesting that tumor-derived IL-1β could substitute for the absence of host IL-1β. The discovery of a novel subpopulation of MDSC prevailing in 4T1/IL-1β-tumor-bearing mice may explain the reported phenotypic differences of MDSC from these mice compared to those from 4T1-tumor-bearing mice 11. It has been reported that splenic MDSC derived from 4T1/IL-1β-tumor-bearing

mice expressed more ROS and were more effective T-cell suppressors 11. We hypothesized that these differences may be attributable to the presence (and predominance) of the Ly6Cneg Paclitaxel purchase MDSC subset. Indeed, we found that Ly6Cneg MDSC expressed higher levels of inducible nitric oxide synthase (iNOS or NOS2) and ROS than Ly6Clow MDSC (Supporting Information Fig. 3A). In line with these observations, we observed that Ly6Cneg MDSC on a per cell basis were significantly more potent buy PLX4032 inhibitors of the proliferation of antigen-activated T cells than Ly6Clow MDSC (Supporting Information Fig. 3B). To study the ability of Ly6Cneg MDSC versus Ly6Clow MDSC to inhibit innate immunosurveillance, we assessed the capacity of 4T1/IL-1β versus 4T1 cells to form solid tumors upon injection into the footpad of BALB/c, BALB/c Rag2−/− (T- and B-cell

deficient) and BALB/c Rag2−/−IL-2Rβ−/− mice (lacking NK cells in addition to T and B cells). While 4T1 cells induced local tumor growth in all mice (Fig. 3A), the kinetics of tumor growth varied in the different recipients. Notably, in BALB/c Rag2−/−IL-2Rβ−/− mice, tumor development was significantly faster than in BALB/c Rag2−/− mice (Fig. 3A), indicating the involvement of NK cells in the delayed tumor growth in the latter.

In contrast, there was no difference in the kinetics of tumor growth upon inoculation of 4T1/IL-1β tumor cells in the various recipients; however, the IL-1β-secreting tumors grew consistently faster than 4T1 tumors in NK-proficient BALB/c Rag2−/− mice (Fig. 3B). Depletion of MDSC using either anti-Gr-1 monoclonal antibodies or Gemcitabine (GEMZAR, 30) resulted in a significant delay of tumor growth in Rag2−/− mice transplanted with 4T1/IL-1β cells (Fig. 3C and data not shown; p<0.05). Together, these data suggested the involvement Idoxuridine of NK cells in the host anti-tumor response and that Gr-1+ cells were involved in the inhibition of the Rag2-independent anti-tumor activity in 4T1/IL-1β-tumor-bearing mice. We analyzed the NK cell compartment in mice bearing established tumors and detected a reduced number (p<0.05) of CD122+NKp46+ NK cells in the bone marrow of 4T1- (30% of control cell numbers) and 4T1/IL-1β-tumor-bearing mice (15% of control cell numbers) (Fig. 4A, left, and Supporting Information Fig. 4). We then analyzed the development of NK cells in the different mice. CD27 is a marker of immature NK cells, while sequential upregulation of CD11b and KLRG-1 expression is associated with NK cell maturation 25.

, 2005). The influence of lactic acid on cytokine production by peripheral blood mononuclear cells (PBMCs) has not RXDX-106 been determined previously, and is the subject of this communication. The findings have biological relevance for an enhanced understanding of infection-related immune mechanisms operative in the lactic acid-dominated female lower genital tract. Venous blood was obtained from 10 healthy female and male volunteers and PBMCs isolated by Ficoll-Hypaque (GE Healthcare Biosciences, Piscataway, NJ) gradient centrifugation. The mononuclear

cell band was recovered, the cells were washed twice in RPMI 1640 culture medium (Invitrogen, Carlsbad, CA) and resuspended in RPMI to a final viable concentration of 1 × 106 cells mL−1. Viability was determined by trypan blue exclusion. The PBMCs were added to the wells of a sterile microtiter plate (1 × 105 cells per well) that contained RPMI medium±various concentrations

of l-lactic acid (Sigma-Aldrich, St. Louis, MO) or l-lactic acid that had been neutralized with sodium hydroxide to the pH of RPMI medium. In other experiments, hydrochloric acid (HCl) was added to RPMI medium to match the pH obtained by lactic acid addition. After incubation for 24 h in a 37 °C, 5% CO2 incubator, either lipopolysaccharide (50 ng mL−1Escherichia coli serotype 0111:B4, Sigma-Aldrich) or an equivalent volume of RPMI was added to quadruplicate wells and incubation Saracatinib mouse was continued for another 24 h. The culture supernatants were then collected by centrifugation and stored at −80 °C until assayed for cytokines. Cell viability as well as the pH in each well were checked at the conclusion of the experiment. All reagents were filter sterilized before use and a sterile technique was used throughout. The study was approved by

the institutional review board of the Weill Cornell Medical Center–New York Presbyterian Hospital and written informed consent was obtained from all participants. The culture supernatants were tested in duplicate for IL-23, IL-12, IL-10, IL-6 and tumor necrosis factor-α (TNF-α) using commercial enzyme-linked immunosorbent Meloxicam assay kits (ebioscience, San Diego, CA for IL-23 and IL-12; Invitrogen for IL-10 and TNF-α; R&D Systems, Minneapolis, MN for IL-6). Experimental values were averaged and converted to pg mL−1 by reference to a standard curve that was generated in parallel to the test samples. The lower limits of sensitivity were 15 pg mL−1 for IL-23, 4 pg mL−1 for IL-12, 0.2 pg mL−1 for IL-10, 9.4 pg mL−1 for IL-6 and 1.7 pg mL−1 for TNF-α. The associations between cytokine levels and incubation condition were analyzed using the Mann–Whitney test. A P value of<0.05 was considered significant. graph pad instat (Graft Pad Software, San Diego, CA) was utilized for the analysis. The addition of lactic acid to PBMCs incubated with lipopolysaccharide resulted in a marked increase in IL-23 secretion over that released in the presence of lipopolysaccharide alone (P=0.0068).

Therefore, the DEC-205 receptor can deliver antigen to DCs for presentation to both CD4+ and CD8+ T cells, and when that is performed in the steady state it leads to deletional tolerance or anergy of the antigen-specific T cells. Targeting steady-state

buy BGB324 immature DCs with antigen-linked anti-DEC-205 antibody, apart from inducing anergy and deletion of cognate T cells [20,35], can also lead to the induction and/or expansion of Tregs[47,82]. Anti-DEC-205/OVA drove short-lived proliferation of OVA-specific CD4+ T cells in vivo and led to the induction of CD25+/CTLA-4+ T cells with regulatory properties which could suppress proliferation and IL-2 production of conventional CD4+ T cells in a dose-dependent manner [82]. This phenomenon was corroborated further in CD4+ and CD8+ T cell-driven hypersensitivity models, where suppression of immune responses could be achieved in vivo by the induction of CD4+CD25+ Tregs by antigen-linked anti-DEC-205. To investigate further whether DCs are able to induce Tregs from truly naive FoxP3- CD4+ T cells, peptide ligands were targeted to DCs through DEC-205 and FoxP3 expression was analysed PLX3397 research buy at the single-cell level [47]. In this study, which used T cells from Rag2−/− TCR transgenic mice to exclude pre-existing FoxP3+ cells, it was shown that the converted Tregs expressed FoxP3 just as

do natural Tregs. It was also demonstrated that minute antigen doses with suboptimal DC activation were necessary for Treg induction, which was enhanced further by the addition of transforming growth factor (TGF)-β or in the absence of IL-2. Importantly, these FoxP3+ Tregs could be expanded by immunogenic presentation of antigen and also retained their surface phenotype and suppressor activity. Recently, Yamazaki and Steinman reported that CD8+DEC205+ splenic DCs are particularly well equipped to induce FoxP3+ Tregs from FoxP3- precursors [45]. This occurs in the presence Pyruvate dehydrogenase of low doses of

antigen and requires TGF-β expressed by the DEC-205+ DCs themselves. This may explain partially why, in some cases, DC targeting by antigen-linked anti-DEC-205 antibody led to the conversion of conventional CD4+ T cells to CD25+CD4+ Tregs[47,82]. The therapeutic potential of DEC-205-mediated antigen delivery has begun to be explored in mouse models of type 1 diabetes [69,70]. The first such study utilized a CD4+ T cell-driven model in which mice express haemagglutinin (HA) under the control of the rat insulin promoter (INS) and an I-Ed-restricted TCR specific for HA110–120. These mice have a diabetes incidence of 40%. When treated with HA peptide-linked anti-DEC-205 repeatedly from birth until 12–16 weeks of age, diabetes was prevented in most animals.

Remove supernatant completely. Critical troubleshooting! This step is the primary cause of non-specific positive results with the secretion assay. Centrifuging cells into a pellet when they are still

warm will contaminate the assay. Keep the cells ice-cold to stop secretion SCH772984 in vivo of cytokines after the secretion period. Ensure that the wash is in buffer, as the ethylenediamine tetraacetic acid (EDTA) helps to stop the reaction Repeat washing step in ice-cold buffer. During the second wash prepare the cytokine detection antibody. This is diluted by adding 20 µl of cytokine detection antibody stock to 80 µl of ice-cold buffer; 100 µl of this stock solution is required per 1 × 107 cells. For example, for 5 × 107 dilute 100 µl of reagent with 400 µl buffer. Store on ice until used. For detection of two cytokines, add 10 µl of each detection antibody per 80 µl buffer.

Critical step– if separating two cytokine populations consecutively, add only one anti-fluorochrome microbead at this point. The second microbead can be added after the first separation: repeat the steps described here. Completely remove supernate. Resuspend in 500 µl buffer. For magnetic labelling, add 100 µl diluted anti-PE or APC microbeads per 1 × 107 cells, mix well and incubate for 15 min at 8°C (i.e. in the refrigerator, not on ice). Critical step– it is essential to have an unseparated sample to work out the start frequency and subsequent recovery of cells. Prepare two MS columns per sample by rinsing PD-1 inhibitor with 500 µl of cold buffer. Place the first column into the magnetic field of a suitable MACS Separator (e.g. MiniMACS). Troubleshooting – it is essential to use two columns. Each column

can enrich the cells about 100 times. Thus, because of the low frequency of cytokine-producing cells, two columns are required to obtain the best Arachidonate 15-lipoxygenase purity. If cells are to be cultured: if cells are to be cultured directly after isolation, cells can also be eluted with culture medium. In this case, replace the last buffer wash with a medium wash, and then elute the cells with medium. If medium is to be used, ensure that it does not contain any particles, e.g. from serum. If in doubt, filter medium before use. If medium elution is used, cells for flow cytometry should be washed free of any phenol red. Critical point.  Do not use any PE- or APC-based tandem fluorochromes to stain cells sorted with anti-PE or APC beads, as they will be bound and stain non-specifically. All cytokine assays are low-frequency analyses. To properly identify cytokine producing cells, both positive staining with, e.g. CD4 or CD8 is required and also exclusion of unwanted cells from the analysis is vital. Exclusion of the dead cells (lymphocyte gating alone is not enough) using propridium iodide (PI), 7-AAD or other vital dyes will virtually eliminate non-specific background staining. It may also be necessary to exclude cells that tend to non-specifically bind fluorochromes, e.g.

Much is still unknown concerning the immunological characterization of these patients. The role of procalcitonin (PCT) and different cytokines has been the most evaluated [3–7]. Deficiency or decreased levels of mannose-binding lectin (MBL), a key

recognition molecule in the complement lectin pathway [8], have been associated with a serious infectious outcome [9–13], selleck kinase inhibitor but the results are controversial [14, 15]. There are several possible reasons for this. MBL deficiency is associated with different phenotypes depending on the status of the rest of the immune system. Experimental animal studies are strictly different from clinical studies, and the clinical studies are often heterogeneous and difficult to compare. Finally, different methods for MBL quantification might give different results and are not directly comparable. The impact of different antibiotic regimens on the immune profiles of febrile neutropenic patients is poorly understood. In this study, constituting a subgroup of patients included in a prospective randomized study [16], we hypothesized that, by blood testing for cytokine levels at the onset of episodes of febrile neutropenia and 1–2 days later in patients undergoing high-dose chemotherapy with stem cell support,

we would find clinically useful prognostic markers for the severity and course of the febrile neutropenic episodes. In addition, we wanted to characterize

the immune responses p38 MAPK inhibitor in these patients. Protein synthesis–active agents, like tobramycin, do have immunomodulatory effects [17]. We also wanted to study whether the dosing regimen of tobramycin, once daily followed by a higher peak concentration versus three times daily followed by a significantly lower peak concentration, affects the cytokine levels. Approximately half of patients received tobramycin once daily and the other half received tobramycin three times daily. Patients, high-dose regimen and blood Mannose-binding protein-associated serine protease samples.  Patients were recruited from one of the institutions participating in a prospective randomized clinical study, comparing tobramycin once versus three times daily, given with penicillin G to febrile neutropenic patients. This study was approved by the local institutional review board and the regional committee for medical research ethics and conducted in accordance with the ethical standards of the Helsinki Declaration (The Regional Committee for Medical Research Ethics, Health Region South, Norway, approved the study protocol on 25 May 2001, reference number S-01111). The informed consent of this study included stating acceptance of supplementary blood samples for later scientific research such as the study we present. All patients had malignant lymphoma and were included between 2001 and 2005 when they developed febrile neutropenia after high-dose chemotherapy with autologous stem cell support.

Other studies show that infants modify their manual actions appropriately to register the features and functions of objects and surfaces they explore (e.g., pliable versus solid, smooth versus textured) (Bourgeois, Khawar, Neal, & Lockman, 2005; Palmer, 1989; Ruff, 1984). Infants’ differential responses to such visual and haptic cues may be indicative of their expanding perception of various surfaces and objects. Given

that we already know that younger infants can visually discriminate between pictures of possible and impossible objects, we now ask whether the perception of anomalous pictorial information compound screening assay in the impossible figure would evoke a differential reaching response in 9-month-old infants. We reasoned that the degree

to which infants manually explore depictions of possible versus impossible objects might provide an index of their interpretation of such displays. Accordingly, we measured differences in the number Selleckchem NVP-BGJ398 of manual behaviors attempted toward realistic photographic displays of possible and impossible cube stimuli that were rich in pictorial depth information (e.g., shading, shadows, texture, color, luminance, and interposition cues). If infants apply their investigative activities with equal frequency to both displays, then this would be interpreted as indiscriminate exploratory action. However, if infants initiate increased exploratory actions toward one of the displays relative to the other, this Vildagliptin would be interpreted as evidence that the perceptual anomaly elicited differential reaching behavior between pictures of possible versus impossible objects. Infants were selected from a public database of new parents and were recruited by letters

and telephone calls. The final sample consisted of 14 9-month-old infants (M age = 283 days, SD = 19.0; 7 boys, 7 girls). An additional four infants were observed but not included in the sample due to lack of attention or excessive fussiness. All infants were full-term with no known developmental difficulties. The visual displays are shown in Figure 1. Each display was constructed by mounting a high-resolution color printout (measuring approximately 13 cm × 13 cm) onto white foam core board that measured approximately 21 cm × 28 cm. Velcro adhesive tape on the back of the board was used to secure each display to the tabletop in front of the infant in an effort to discourage the infants from trying to pick up the board. The stimulus displays of primary interest were the realistic color photograph of a structurally possible wooden cube and that of an impossible cube. The image of the impossible wooden cube was created in Photoshop® (Adobe Systems, Inc., San Francisco, CA) by altering the local depth relations in a single overlapping bar junction. The color photograph displays of possible and impossible cubes were used previously in a visual discrimination task with 4-month-olds (Shuwairi et al., 2007).

33 The overall utility of this type of assessment requires more investigation and remains experimental at this stage. Crossmatching is a vital tool in assessing the immune compatibility of a particular donor/recipient pairing. A positive T-cell CDC crossmatch click here would usually mean that a particular pairing should not proceed. In some cases, a desensitization protocol may allow such a transplant to occur, avoiding hyperacute

or early acute rejection albeit with inferior long-term graft outcomes compared with patients who are not sensitized to their donor. The advent of flow crossmatching and Luminex assays has allowed detection of lower titre but potentially clinically relevant anti-HLA antibodies by approximately 10-fold. Further studies are required to better selleck products define the significance of very low-level DSAbs, non-complement fixing antibodies, IgM antibodies

and non-HLA antibodies as well as the importance of assessing T cellular sensitization. The authors’ view is that the tried and trusted technique of CDC crossmatching remains essential and should be coupled with a determination of the specificity of anti-HLA antibodies by Luminex. With these two assays the role of flow crossmatching is less clear and is rarely helpful in decision making. The ideal future crossmatch will be highly sensitive in identifying DSAbs and provide accurate prediction of the functional significance of the antibody. This will allow transplant physicians to confidently proceed with a transplant in the face of a clinically irrelevant DSAb while providing clear prognostic information in the setting of more serious Methane monooxygenase antibodies. We thank Dr Kevan Polkinghorne for his critical appraisal of the manuscript. “
“Date written: Jan 2008 Final submission: June 2008 No recommendations possible based on Level I or II evidence (Suggestions are based on Level III and IV evidence) Potential

living donors should have their urinary protein excretion measured using either a 24-hour urine collection (daily excretion) or a spot urine sample (protein/creatinine ratio). Short- and long-term living kidney donor outcomes need to be closely monitored. The aim of this guideline is to review the available literature on the potential long-term risks of donating a kidney in the presence of pre-donation proteinuria and to develop suggestions for management of these potential donors. The justification for performing living kidney donation is based on the benefits of the procedure on the recipient’s health and on the psyche of the donor through the act of altruism, outweighing the short- and long-term adverse outcomes on the donor. In the medical assessment of the potential donor, a critical estimation is made of their future risk of kidney failure and cardiovascular disease. If the risk is predicted to be too great then the living kidney donation does not proceed.

gondii by flow cytometry. The mRNA and protein expression levels of transforming growth factor-β (TGF-β) and interleukin-17A (IL-17A) were analyzed using real-time Selleck Palbociclib PCR and enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of forkhead box P3 (Foxp3), retinoic acid–related orphan receptor γt (RORγt), and IL-6 were also

analyzed using real-time PCR. The correlations of the ratio of Treg/Th17 to the mRNA or protein expression level of those factors were analyzed by Spearman’s correlation analysis. Data were analyzed by unpaired t-test and paired t-test. Results  The proportion of Tregs or Th17 cells in the placenta and spleens of the T. gondii-infected pregnant mice was significantly lower or higher than in those of non-infected mice, respectively. Upregulation of TGF-β and downregulation of IL-17A were found in the placenta of T. gondii-infected pregnant mice. The ratio of Treg to Th17 was significantly lower in the infected mice than that in the non-infected mice (P < 0.01).The ratio of Treg to Th17 positively or negatively correlated with the protein expression level of TGF-β (r = 0.6204,

P < 0.05) or IL-17A (r = −0.6296, P < 0.05), respectively. The ratio also positively correlated with the mRNA expression level of Foxp3 Volasertib order (r = 0.7985, P < 0.01), but negatively correlated with the mRNA expression level of RORγt (r = −0.6153, Rutecarpine P < 0.05), and IL-6 (r = −0.7492, P < 0.01). Conclusion  TheTreg/Th17 imbalance exists in the pregnant mice infected with T. gondii, which is associated with the expression of related cytokine and key transcription factors. This result suggests that the embryo loss caused by this parasite may be associated with a reduced ratio of Treg to Th17 cell number. "
“Defective control of T cell apoptosis is considered to be one of the pathogenetic mechanisms in systemic lupus erythematosus (SLE). Oestrogen has

been known to predispose women to SLE and also to exacerbate activity of SLE; however, the role of oestrogen in the apoptosis of SLE T cells has not yet been documented. In this study, we investigated the direct effect of oestrogen on the activation-induced cell death of T cells in SLE patients. The results demonstrated that oestradiol decreased the apoptosis of SLE T cells stimulated with phorbol 12-myristate 13-acetate (PMA) plus ionomycin in a dose-dependent manner. In addition, oestradiol down-regulated the expression of Fas ligand (FasL) in activated SLE T cells at the both protein and mRNA levels. In contrast, testosterone increased FasL expression dose-dependently in SLE T cells stimulated with PMA plus ionomycin. The inhibitory effect of oestradiol on FasL expression was mediated through binding to its receptor, as co-treatment of tamoxifen, an oestrogen receptor inhibitor, completely nullified the oestradiol-induced decrease in FasL mRNA expression.

Experimentally, however, it is often difficult to discriminate direct effects of antigenic stimulation on recruitment processes from indirect effects CH5424802 where a few antigen-specific T cells (‘pioneer

cells’60) are required to boost (non-specific) recruitment of T cells into the tissue. Costimulatory signals (such as those mediated by CD28) delivered to T cells, in conjunction with TCR engagement, are required to sustain T-cell division, differentiation and survival.61–63 Negative costimulators [such as cytotoxic T-lymphocyte antigen 4 (CTLA-4)] counteract these effects, thus promoting homeostatic mechanisms and preventing autoimmunity. These costimulators have been shown to regulate adhesion molecules and intracellular mediators of cytoskeletal rearrangement in vitro.64–70 In vivo, CD28-mediated signals promote the localization of T cells to target tissue following priming. A prominent feature of CD28-deficient immune responses is the inefficient localization of primed T cells to non-lymphoid antigenic sites.61,71,72 We recently reported that intact CD28 signalling is required for primed T cells to leave lymphoid tissue and migrate to antigenic

sites following priming.73 click here TCR-transgenic T cells carrying a mutation in the cytoplasmic tail of CD28 (CD28Y170F) that abrogates phosphatidylinositol-3-kinase (PI3K) recruitment, without leading to defects in clonal expansion,74 failed to localize to target tissue following priming. The mechanism by which CD28 promotes migration of primed T cells to target tissue is unclear. CD28 does not appear to directly mediate adhesion,75 but may favour primed T-cell migration to non-lymphoid tissue by inducing integrin-mediated adhesion.73 The long-term effect of CD28-mediated signals on T-cell migration73 suggests that additional mechanisms, such as transcriptional regulation of chemokine

receptor expression,76 are likely to be involved. Despite sharing these adhesion-inducing and pro-migratory properties in vitro,77 CTLA-4-mediated signals Selleckchem 5-FU lead to effects antagonistic to those induced by CD28 on T-cell migration in vivo. CTLA-4 ligation reduced conjugate formation with cognate DCs and their retention in lymph nodes in response to antigen, suggesting that CTLA-4 engagement may limit the expansion of specific T cells by reducing their cumulative interactions with cognate DCs. In addition, tissue infiltration by a murine HY-specific H2-Kk-restricted T-cell clone was abrogated by CTLA-4 ligation,73 suggesting that CTLA-4 engagement can antagonize recruitment of primed T cells to target tissue mediated by antigen-induced signals. A number of costimulatory molecules other than CD28 and CTLA-4 have been implicated in the regulation of memory T-cell migration.

8 The use of herbal medicine has increased in developed countries.9 Alternative remedies are perceived to be innocuous and may provide placebo effects from the rituals associated with their ingestion.10 Use of herbal medicines increased in the USA by 25% between 1990 and 1997.11 Approximately 10% of US adults were using herbal remedies in 1999. Approximately $US 4.2 out of the $US 17.8 billion spent on ‘dietary supplements’ in 2001 were for herbs and other botanical remedies.12 Approximately $US 5 billion worth of over-the-counter Sunitinib in vivo herbal medicines were sold in the European countries in 2003.13 Herbal medicine accounted for approximately

26% of all alternative and complimentary medicine use in Australia.14 The global annual turnover in herbal medicines is estimated at $US60 billion, representing approximately 20% of the overall drug market.15 The nephrotoxic potential of herbal remedies is being increasingly recognized.3,16,17 Causality is suspected on the basis of a temporal association between the intake of an agent and the injury. This is easier to establish in the case of acute toxicity where the interval between intake and presentation is short and the history of use of the offending agent is easy to recall, but harder in chronic

diseases that progress slowly. Remote exposure may be forgotten or even denied for fear of social stigmatization. Herbal toxicity can develop in any of the following situations:3,18,19 Selleck Palbociclib (i) consumption of a herb with unknown toxicity; (ii) incorrect identification leading to substitution of an innocuous herb with a toxic one; (iii) deliberate or inadvertent contamination with nephrotoxic non-herbal drugs (e.g. non-steroidal anti-inflammatory agents), pesticides or chemicals (e.g. heavy metal contamination from soil or water); (iv) potentiation of the toxic effect

of a conventional drug due to interaction with a compound MRIP present in the herb; and (v) consumption of meat from an animal that has grazed on toxic plants (e.g. hemlock). The kidney is the route of excretion of most of the substances present in the herbs. The high blood flow rate and large endothelial surface area of the kidneys ensures delivery of large amounts of toxin to the renal parenchyma. High concentrations may be reached in the medulla because of active tubular transport, especially during a state of fluid deprivation. Renal involvement associated with the use of traditional medicinal products can take several forms,16–18 including acute kidney injury, tubular function defects, dyselectrolytaemias, systemic hypertension, chronic kidney disease (CKD), renal papillary necrosis, urolithiasis and urothelial cancer.