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latter findings were neither incorrect nor coincidental. Because of the risk of recurrence of anti-GBM disease in a transplant kidney [3], transplantation with a kidney from his spouse was postponed until 6 months after disappearance of anti-GBM antibodies. Patient was advised to seek other employment, because in our opinion it is mandatory to avoid future exposition to hydrocarbons or other toxins. In conclusion, we report for the first time since 1984 the association between Goodpasture and TTP, corroborating the existence of such an association. Conflict of interest statement. None declared. 1
1. Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG. Alport’s Syndrome, Goodpasture’s Syndrome, and Type IV Collagen. N Engl J Med 2003; 348: 2543–2556 2. Stave GM, Croker BP. Thrombotic microangiopathy in antiglomerular basement membrane glomerulonephritis. Arch Pathol Lab Med 1984; 9: 747–751 3. Netzer KO, Merkel F, Weber M. Goodpasture syndrome and end-stage renal failure–to transplant or not to transplant? Nephrol Dial Transplant 1998; 13: 1346–1348 doi:10.1093/ndt/gfm483 Advance Access publication 22 September 2007 See http://www.oxfordjournals.org/our_journals/ndtplus/
Does desacyl ghrelin contribute to uraemic anorexia? Sir, A study investigating the possible role of desacyl ghrelin in uraemic anorexia was published recently in the American Journal of Nephrology [1]. This study by Muscaritoli et al. shows that desacyl ghrelin levels were significantly higher in anorexic than in non-anorexic haemodialysis patients, suggesting that desacyl ghrelin may be involved in the pathogenesis of uraemic anorexia. However, this study raises the question of how desacyl ghrelin may induce anorexia in haemodialysis patients. Indeed, there is strong evidence that desacyl ghrelin, like ghrelin, functions as orexigenic peptides in the hypothalamus [2]. Very recently, in an elegant experimental study, Toshinai et al. [2] demonstrated that intracerebroventricular administration of desacyl ghrelin to rats or mice fed ad libitum significantly stimulated feeding during the light phase [2]. In addition, neither intraperitoneal nor intracerebroventricular administration of desacyl ghrelin to fasting mice suppressed fasting. Toshinai et al. also showed that the
intracerebroventricular administration of desacyl ghrelin induces the expression of Fos, a marker of neuronal activation, in orexin-expressing neurons, and increased locomotor activity, suggesting that that desacyl ghrelin may increase wakefulness and locomotor activity for food seeking by stimultating orexin neurons. Finally, the study of Toshinai et al. documented the fact that central administration of desacyl ghrelin to GHS-R-deficient mice stimulates feeding, suggesting that desacyl acts on a target protein that is specific for desacyl ghrelin and independent of the GSH-R. In contrast with these results are those of the study by Asakawa et al. [3], which suggest that desacyl ghrelin induces a negative energy balance by decreasing food intake and delaying gastric emptying. Indeed, in the study by Asakawa et al., the administration of desacyl ghrelin into the third central ventricle reduced food intake in food-deprived mice but not in non-food-deprived ones [3]. To further support the hypotheses that acylated and desacyl ghrelin play different roles in the regulation of food intake, Muscaritoli et al. cited the study of Aguilera et al. [4], demonstrating that acylated ghrelin is lower in anorexic than in non-anorexic uraemic patients undergoing peritoneal dialysis. Indeed, also in this field, data are conflicting [4,5]. Chang et al. [5] have determined the profile of plasma ghrelin levels over 24 h in non-diabetic haemodialysis patients, showing a unique diurnal change without an obvious plasma ghrelin rise before each meal nor a rapid fall after eating. They also found that the average level of plasma ghrelin in haemodialysis patients was one-fifth higher than in the healthy control group at most sampling times during the day, except between 10 p.m. and 2 a.m. According to the authors of the study, these observations suggest that there is a resistance to ghrelin action in end-stage renal disease patients, either peripheral or central or both. The detection of high plasma ghrelin levels in haemodialysis patients is in contrast to the strong tendency of these patients to be anorexic [5]. Recently, we measured the circulating levels of ghrelin in 51 haemodialysis patients in our laboratory, without detecting statistically significant differences between patients with very poor, poor, fair, good or very good appetite (personal communication). The pathogenesis of anorexia in haemodialysis patients is essentially unknown. It has been proposed that uraemic toxins as middle molecules, inflammation, altered amino acid pattern, hormones (e.g. leptin and ghrelin) and neuropeptides (e.g. neuropeptide Y) are involved [6]. However, the studies of recent years have suggested that the simple and mechanical transmission of results obtained in experimental studies cannot be applied directly in humans and in clinical practice [7–9]. As an example, against the evidence of experimental studies [10], we demonstrated in the laboratory of the Department of Surgery of our University that serum leptin does not play a major pathogenetic role in anorexia of haemodialysis patients [8], suggesting that a state of relative leptin resistance may occur in patients with end-stage renal disease [9]. The pathogenesis of anorexia in uraemic patients remains an enigma, although it continues to have detrimental effects on nutritional status, quality of life and survival. Servizio Emodialisi, Istituto di Clinica Chirurgica Universita` cattolica del sacro Cuore Roma, Italia Email:
[email protected]
Maurizio Bossola Stefania Giungi Luigi Tazza Giovanna Luciani
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Wim Terryn1,2 Department of Nephrology Dominique Benoit3 Regionaal Ziekenhuis Jan Yperman Ypres Ann Van Loo1 2 Ghent University Hospital Patrick Peeters2 3 Department of Intensive Care Hans Schepkens4 Ghent University Hospital Kristof Cokelaere5 4 Department of Nephrology Raymond Vanholder2 Heilig Hartziekenhuis Roeselare 5 Department of Pathology Regionaal Ziekenuis Jan Yperman Ypres, Belgium Email:
[email protected]
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doi:10.1093/ndt/gfm505 Advance Access publication 26 July 2007 See http://www.oxfordjournals.org/our_journals/ndtplus/
A typical presentation of cutaneous leishmaniasis after renal transplantation Sir, Leishmania parasites are transmitted to humans through the bite of sand flies and may cause visceral, cutaneous or mucocutaneous disease, with clinical features ranging from localized ulcers to systemic lethal disease. The mucocutaneous form is mostly found in Latin America and millions of people live in areas of active parasite transmission [1]. A 49-year-old female transplant recipient under immunosuppressive treatment developed multiple erythematous and painful lesions on the legs (Figure 1A). The diagnosis of leishmaniasis was confirmed by enzyme-linked immunoassay, immunofluorescence assay and immunohistochemistry, as well as by multiplex polymerase chain reaction (PCR) analysis as previously described [2]. Leishmania amastigotes were present in the lesions and PCR analyses revealed parasites from the L. braziliensis complex (Figure 1B). By conventional reverse transcriptase-PCR reaction (RT-PCR) [3] expression of IL-4 (Figure 1C) and IL-13 (Figure 1D) mRNA was demonstrated and IFN-gamma mRNA (Figure 1E) was not detected in the wound tissue. After 50 days, the wounds completely healed after treatment with amphotericin B [4]. No relapses were observed after 18 months of maintaining normal renal function. Treatment with amphotericin B was efficient and safe in the case studied, while the patient was taking a calcineurin inhibitor. Thus, in endemic areas for leishmaniasis, atypical skin lesions
Fig. 1. (A) Detail of an erythema present on the patient’s leg. (B) Multiplex PCR analysis (MW), 100 bp molecular weight marker; lane 1, L. braziliensis complex (149 bp); lane 2, L. mexicana complex (218 bp); lane 3, L. donovani complex (351 bp), lane 4, negative control (no DNA); lane 5, T. cruzi DNA sample; lane 6, patient’s sample. (C–E), Conventional RT-PCR analyses for IL4 (437 bp), IL13 (342 bp) and IFNg (257 bp) expression. MW, 100 bp molecular weight marker; lanes 1 and 2, negative (no cDNA) and positive controls, respectively; lane 3, patient’s sample. GAPDH, Glyceraldehyde 3-phosphate dehydrogenase, used as internal control.
in immunosuppressed patients should be investigated for the presence of Leishmania parasites. Acknowledgement. This work was supported by CNPq, Brazil and by a grant from the Sustainable Sciences Institute (SSI), USA, to M.A.S. 1 Servico de Nefrologia da Santa Casa de Goiania, Goiania, GO, Brazil 2 Instituto de Ciencias Biomedicas da Universidade Federal de Uberlandia, Uberlandia, MG, Brazil Email:
[email protected]
Fernando A. Vinhal1 Sandra R. Afonso-Cardoso2 Adriano G. Silva2 Cristiano G. Pereira2 Waldir Sousa1 Silvia M. Botelho1 Joao B. S. Souza1 Wellinton D. Silva1 Janethe D. O. Pena2 Maria A. Souza2
1. Alvar J, Yactayo S, Bern C. Leishmaniasis and poverty. Trends Parasitol 2006; 22: 552–557 2. Harris E, Kropp G, Belli A, Rodriguez B, Agabian N. Singlestep multiplex PCR assay for characterization of new world Leishmania complexes. J Clin Microbiol 1998; 36: 1989–1995 3. Gomes MA, Rodrigues FH, Afonso-Cardoso SR et al. Levels of immunoglobulin A1 and messenger RNA for interferon-gamma and tumor necrosis factor-alpha in total saliva from patients with diabetes mellitus type 2 with chronic periodontal disease. J Periodontal Res 2006; 41: 177–183 4. Davidson RN. Practical guide for the treatment of leishmaniasis. Drugs 1998; 56: 1009–1018 doi:10.1093/ndt/gfm520
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1. Muscaritoli M, Molfino A, Chiappini MG et al. Anorexia in hemodialysis patients: the possibile role of des-acyl ghrelin. Am J Nephrol 2007; 27: 360–365 2. Toshinai K, Yamaguchi H, Sun Y et al. Des-acyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor. Endocrinology 2006; 147: 2306–2314 3. Asakawa A, Inui A, Fujimiya M et al. Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin. Gut 2005; 54: 18–24 4. Aguilera A, Cirugeda A, Amair R et al. Ghrelin plasma levels and appetite in peritoneal dialysis patients. Adv perit Dial 2004; 20: 194–199 5. Chang CC, Hung CH, Yen CS et al. The relationship of plasma ghrelin level to energy regulation, feeling and left ventricular function in non-diabetic hemodialysis patients. Nephrol Dial Transplant 2005; 20: 2172–2177 6. Bossola M, Tazza L, Giungi S, Luciani G. Anorexia in hemodialysis patients: an update. Kidney Int 2006; 70: 417–422 7. Wiecek A. How does leptin contribute to uraemic cachexia? Nephrol Dial Transplant 2005; 20: 2620–2622 8. Bossola M, Muscaritoli M, Valenza V et al. Anorexia and serum leptin levels in hemodialysis patients. Nephron Clin Practice 2004; 97: c76–c82 9. Bossola M. Does leptin conribute to uraemic cachexia? Nephrol Dial Transplant 2006; 21: 1125–1126 10. Cheung W, Yu PX, Little BM et al. Role of leptin and melanocortin signalling in uremia-associated cachexia. J Clin Invest 2005; 115: 1659–1665
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