Immunological Approaches in the Treatment of Diabetic Nephropathy.

Diabetic nephropathy (DN), the leading cause of end-stage renal disease, has no definite treatment so far. In fact, a combination of metabolic, hemodynamic, and immunological factors are involved in the pathogenesis of DN; therefore, effective disease management requires a holistic approach to all predisposing contributors. Due to the recent findings about the role of inflammation in the initiation and progression of kidney injury in diabetic patients and considerable advances in immunotherapy methods, it might be useful to revise and reconsider the current knowledge of the potential of immunomodulation in preventing and attenuating DN. In this review, we have summarized the findings of add-on therapeutic methods that have concentrated on regulating inflammatory responses in diabetic nephropathy, including phosphodiesterase inhibitors, nuclear factor-kB inhibitors, Janus kinase inhibitors, chemokine inhibitors, anti-cytokine antibodies, cell therapy, and vaccination.

Expression of Programmed Cell Death 1 and Helios Genes Correlates With rs872071A>G and rs12203592C>T Single-Nucleotide Polymorphisms of InterferonRegulatory Factor 4 in Patients with T-Cell-Mediated Rejection of Renal Allograft.

OBJECTIVES: Acute T-cell-mediated rejection of the renal allograft is a serious posttransplant challenge that requires administration of high-dose immunosuppressive drugs with considerable side effects; therefore, specific targeting of T-cell responses may improve both prevention and treatment of T-cell-mediated rejection. A potential candidate for this purpose is interferon regulatory factor 4 because of its implication in differentiation and function of T cells. Our aim was to evaluate the frequency of the rs872071A>G and rs12203592C>T single-nucleotide polymorphisms of the interferon regulatory factor 4 gene and association of these 2 polymorphisms with the gene expression of programmed cell death 1 and Helios in patients with T-cell-mediated rejection versus stable recipients. MATERIALS AND METHODS: Sixty recipients with T-cell- mediated rejection and 60 age-matched and sex-matched stable recipients were recruited. Two single-nucleotide polymorphisms of interferon regulatory factor 4 gene, as well as the expression of programmed cell death 1 and Helios genes in peripheral blood mononuclear cells, were investigated with real-time polymerase chain reaction. RESULTS: Programmed cell death 1 gene expression was reduced in patients with T-cell-mediated rejection versus stable recipients (P = .03). The frequency of rs872071A>G and rs12203592C>T single-nucleotide polymorphisms showed no significant difference between groups. Presence of the rs12203592C>T single-nucleotide polymorphism was directly correlated with the expression of programmed cell death 1 gene (P = .049), and rs872071A>G positivity was directly correlated with Helios gene expression (P = .008), which suggests an inhibitory role for interferon regulatory factor 4 on programmed cell death 1 and Helios molecules. CONCLUSIONS: Programmed cell death 1 gene expression was lower in patients with T-cell-mediated rejection versus stable recipients. Low-expressing singlenucleotide polymorphisms of interferon regulatory factor 4 could enhance the downstream gene expression of programmed cell death 1 and Helios immunoregulatory molecules. Therefore, specific inhibition of interferon regulatory factor 4 may promote tolerance induction in the allograft.

Comparing IRF-4 Gene Expression Between Acute T cell- Mediated Rejection and Stable Renal Transplant Recipients.

INTRODUCTION: Renal transplant rejection is one of the clinical challenges, which usually requires administration of immunosuppressive drugs causing serious side effects. Therefore, invention of effective and specific therapeutics is necessary to control undesired immune responses particularly T-cell reactions to allograft. Interferon Regulatory Factor-4 (IRF-4) due to its implication on T cells differentiation and function might be targeted to treat T cell-mediated cellular rejection (TCMR). The aim of this study was to investigate the association between IRF-4 gene expression and acute TCMR, as well as to examine the correlation between IRF-4 gene expression and cellular expression of Programmed cell death-1 (PD-1) and Helios molecules. METHODS: Peripheral blood samples were obtained from 30 patients with biopsy proven acute TCMR and 30 stable recipients. IRF-4 gene expression was quantified using RT-PCR, and cellular expression of PD-1 and Helios were evaluated with flowcytometry. RESULTS: IRF-4 gene expression was significantly increased in acute TCMR patients compared with stable recipients (P < .05). Helios protein expression was slightly decreased in TCMR group but this was not statistically significant. There was a negative correlation between IRF-4 gene expression and PD-1 as well as Helios frequency in the whole studied population. CONCLUSION: IRF-4 expression increases in acute TCMR which might also lead to a diminished expression of downstream immunoregulatory molecules such as PD-1 and Helios. Therefore, specific inhibition of IRF-4 may be helpful in managing acute TCMR.

Investigating the Role of BAFF and Its Receptors in Renal Transplant Recipients with Chronic Antibody-Mediated Rejection.

BACKGROUND: Kidney transplantation is the best treatment option for end stage renal disease (ESRD), but graft rejection is still a big obstacle that occurs in spite of immunosuppressive therapy. B cells are considered as the major reason for renal graft rejection because of antibody production. Due to their roles in B cell function, we intended to evaluate the B cell activating factor (BAFF) and its receptors including BAFF receptor (BAFF-R), B cell maturation antigen (BCMA), and transmembrane activator and cyclophilin ligand interactor (TACI) in renal transplant patients. METHOD: The study included 40 kidney allograft patients with cAMR, 40 stable kidney allograft patients, and 8 healthy volunteers with normal kidney function. The percentage and absolute number of CD19+ B cells were analyzed by flow cytometry, the serum level of BAFF was analyzed by ELISA, and mRNA expressions of BAFF and BAFF receptors (BAFF-R, BCMA, and TACI) were measured using quantitative real-time PCR. RESULTS: The percentage and the absolute number of B cells decreased significantly in stable and cAMR patients compared to healthy individuals. The serum level and gene expression of BAFF, as well as the mRNA level of BCMA, were increased significantly in both cAMR and stable patients compared to healthy volunteers. There was an overexpression of TACI mRNA in cAMR patients compared to stable patients. CONCLUSIONS: Both soluble protein and mRNA transcript of BAFF increased in transplant recipients. However, BAFF neither at the serum level nor at the mRNA transcript level cannot be a good biomarker for the prediction of cAMR. In addition, expression of TACI, compared to other receptors of BAFF, confers a potential to be used in distinguishing cAMR and stable kidney transplant patients.

TLR-2, TLR-4 and MyD88 genes expression in renal transplant acute and chronic rejections.

BACKGROUND: Graft rejection due to alloreactivity is still the main obstacle to successful renal transplantation. Toll-like receptors (TLRs), which are significantly involved in initiating inflammation, triggering innate immunity, occurrence of ischaemia reperfusion injury (IRI) and subsequent deterioration of allograft function, are of interest in molecular diagnosis of graft rejection. METHODS: In present research, we have evaluated the mRNA expressions of TLR-4, TLR-2 and myeloid differentiation primary response gene 88 (MyD88) in peripheral blood mononuclear cells (PBMCs) and biopsy samples of 26 stable graft function (SGF), 14 acute T-cell-mediated rejection (ACMR), six acute antibody-mediated rejection (AAMR), 10 chronic T-cell-mediated rejection (CCMR) and four chronic antibody-mediated rejection (CAMR) cases of renal transplant recipients, using TaqMan detector real-time polymerase chain reaction (RT-PCR). RESULTS: It was found that TLR4 mRNA level was significantly elevated in PBMCs of both ACMR (P.v: 0.025) and CCMR (P.v: 0.007) cases, while TLR2 gene was upregulated only in PBMCs of ACMR (P.v: 0.024). Moreover, MyD88 expression was increased in biopsy samples of all rejection groups AAMR (P.v: 0.032), ACMR (P.v: 0.002), CAMR (P.v: 0.038) and CCMR (P.v: 0.013) and could distinguish them from stable grafts with AUC (area under curve) of 0.81, 0.80, 0.83 and 0.77, respectively. CONCLUSION: These data showed that MyD88 gene upregulation in renal tissue could have diagnostic value and increased level of TLR4 mRNA in PBMCs could be suggestive of cell-mediated rejections. Therefore, monitoring the expression level of inflammatory signalling genes might be useful in predicting allograft rejection.

Effects of pioglitazone on blood glucose and inflammatory markers of diabetic kidney transplant patients: a randomized controlled trial.

INTRODUCTION: The aim of this study was to assess the effects of pioglitazone on blood glucose control and inflammatory biomarkers in diabetic patients receiving insulin after kidney transplantation. MATERIALS AND METHODS: In a randomized placebo-controlled trial, 62 diabetic kidney transplant patients were followed for 4 months after randomly assigned to placebo and pioglitazone (30 mg/d) groups. All of the patients continued their insulin therapy irrespective of the group that they were assigned to, in order to evaluate the effects of addition of pioglitazone on blood glucose and inflammation biomarkers including serum C-reactive protein, high-sensitivity C-reactive protein, and interleukin-18 levels, as well as erythrocyte sedimentation rate. RESULTS: At baseline, there were no significant differences in laboratory studies between the two groups. After 4 months of intervention, along with significant improvement in hemoglobin A1c in the pioglitazone group, daily insulin requirements also decreased and lipid profile improved significantly. In addition, erythrocyte sedimentation rate, C-reactive protein, and high-sensitivity C-reactive protein values were significantly lower in the pioglitazone group (P = .03, P < .001, and P = .01). Interleukin-18 levels were not significantly different at the end of the study between the two groups, but it had a decreasing trend in the pioglitazone group (P = .002). CONCLUSIONS: Pioglitazone complementing insulin in diabetic kidney transplant patients not only improved glycemic control, evidenced by hemoglobin A1c, and reduced daily insulin requirement, but also decreased inflammatory markers which may have an impact on overall cardiovascular events and mortalities beyond glycemic control.

Prevalence and risk factors of recurrent cytomegalovirus infection in kidney transplant recipients.

INTRODUCTION: Recurrence of cytomegalovirus (CMV) infection following solid organ transplantation causes mortality and morbidity in allograft recipients. The aim of this study was to evaluate prevalence and risk factors of recurrent CMV infection in kidney transplant patients. MATERIALS AND METHODS: Four hundred and twenty-seven consecutive kidney transplant recipients were included in this retrospective cohort study. Both donors and recipients were CMV seropositive. Recurrent CMV infection (symptomatic or asymptomatic) was defined as detection of CMV infection in a patient who has had previously documented infection and who had not have virus detected for an interval of at least 4 weeks during active surveillance. RESULTS: Of 427 recipients, 71 (16.6%) had CMV infection, of which 19 (4.4%) were recurrent infection. Donor source, dialysis duration before transplantation, recipient and donor age and sex, and administration of antithymocyte globulin and prophylactic treatment ganciclovir were not associated with CMV infection or recurrence. The use of tacrolimus in the immunosuppressive regimen as compared to cyclosporine was an independent risk factor for CMV infection but not recurrent infection. CONCLUSIONS: Intensive immunosuppressive regimen, such as using tacrolimus, might be associated with a higher risk for CMV infection, but this study was not able to document the same association for recurrent CMV disease. In patients receiving immunosuppressive regimens that include tacrolimus and antithymocyte globulin, prophylactic treatment for CMV disease with ganciclovir is recommended.

The frequency of HHV-8 infection in otherwise healthy blood donors as well as renal allograft recipients living in Iran.

BACKGROUND: Different reports from Middle East countries demonstrated Kaposi's sarcoma (KS) in transplant population. This vascular malignancy occurs mostly among immunocompromised individuals. Human herpesvirus 8 (HHV-8) appears to be the causative factor for the development of this neoplasm. Transplant programs are concerned about the frequencies of HHV-8 infection either in general population or transplant patients. METHODS: The current study was conducted in two phases. Firstly, we detected antibodies against HHV-8 in 790 otherwise healthy blood donors. Secondly, a total of 125 kidney allograft recipients evaluated as being seropositive for HHV-8. We utilized enzyme immunoassay (EIA) for serologic studies. RESULTS: Among blood donors, the male to female ratio was 1.05 (405 vs. 385 ) while the mean age was 38.9 ± 11.7 years. The serostatus of none of these blood donors were positive for HHV-8. Among kidney recipients, the male to female ratio was 1.9 (82 vs. 43). The mean age was 39.01 ± 14.77 years. Two (1.6%) patients were seropositive for HHV-8. CONCLUSION: The prevalence of HHV-8 infection among Iranians is likely to be low. Yet, owing to the evidence of this infection among kidney allograft recipients and its probable role in developing post- transplantation KS (PT-KS), further studies appear to be required to keep the various aspects of this infection under close surveillance.

Sirolimus versus calcineurin inhibitor-based immunosuppressive therapy in kidney transplantation: a 4-year follow-up.

INTRODUCTION: Sirolimus is the one of new immunosuppressants that may be a substitute to traditional drugs such as cyclosporine. We present our investigation on sirolimus-based immunosuppression in kidney transplant recipients as compared with cyclosporine-based immunosuppression. MATERIALS AND METHODS: We enrolled 100 patients in an open-labeled randomized clinical trial at Shahid Labbafinejad Medical Center. The patients were assigned to one of the immunosuppressive groups to receive either sirolimus or cyclosporine in combination with mycophenolate mofetil and steroids. All kidney transplant recipients were followed up by for serum creatinine and glomerular filtration rate for 4 years. RESULTS: There was no significant differences between the two groups regarding serum creatinine level and GFR until for years posttransplant; however, serum creatinine levels were significantly lower and the GFRs were higher in the sirolimus group after 3 and 4 years. The mean serum creatinine was 1.24 ± 0.28 mg/dL in the sirolimus group and 1.57 ± 0.33 mg/dL in the cyclosporine group at 4 years posttransplant (P = .02). Also, GFR was 79.8 ± 22.3 mL/min/1.73 m2 in the sirolimus group and 70.3 ± 23.6 mL/min/1.73 m2 in the cyclosporine group B (P = .04). Acute rejection was 1.7-fold higher in the cyclosporine group than in the sirolimus group. CONCLUSIONS: Our study demonstrated that sirolimus in the immunosuppressive regimen of kidney transplant recipients had better outcomes regarding graft and patient survival. The effectiveness of sirolimus for kidney allograft recipients should be further assessed to be implemented from the first day after transplantation.

Incidence of malignancy after living kidney transplantation: a multicenter study from iran.

Malignancy is a common complication after renal transplantation. However, limited data are available on post-transplant malignancy in living kidney transplantation. Therefore, we made a plan to evaluate the incidence and types of malignancies, association with the main risk factors and patient survival in a large population of living kidney transplantation. We conducted a large retrospective multicenter study on 12525 renal recipients, accounting for up to 59% of all kidney transplantation in Iran during 22 years follow up period. All information was collected from observation of individual notes or computerized records for transplant patients. Two hundred and sixty-six biopsy-proven malignancies were collected from 16 Transplant Centers in Iran; 26 different type of malignancy categorized in 5 groups were detected. The mean age of patients was 46.2±12.9 years, mean age at tumor diagnosis was 50.8±13.2 years and average time between transplantation and detection of malignancy was 50.0±48.4 months. Overall tumor incidence in recipients was 2%. Kaposis' sarcoma was the most common type of tumor. The overall mean survival time was 117.1 months (95% CI: 104.9-129.3). In multivariate analysis, the only independent risk factor associated with mortality was type of malignancy. This study revealed the lowest malignancy incidence in living unrelated kidney transplantation.

Effect of erythropoietin on kidney allograft survival: early use after transplantation.

INTRODUCTION: Erythropoietin is administered for treatment of anemia in chronic kidney disease and kidney transplantation. Erythropoietin improves oxygenation of organs and prevents them against apoptosis. The aim of this study was evaluation of erythropoietin's effect on graft survival in the early phase after transplantation. MATERIALS AND METHODS: Forty kidney transplant candidates with a hemoglobin level of 8 g/dL to 10 g/dL were randomized to receive either erythropoietin (PD-Poietin) or placebo for the first posttransplant week. They were followed up for 6 months and serum creatinine levels, glomerular filtration rate (GFR), allograft rejection episodes, and graft loss were compared between the two groups. RESULTS: The mean creatinine level and GFR were 1.16 ± 0.03 mg/mL and 85.1 ± 18.3 mL/min in the erythropoietin group and 1.2 ± 0.2 mg/dL and 83.3 ± 21.1 mL/min in the control group at baseline. After 6 months of follow-up, the mean of creatinine level and GFR reached to 1.11 ± 0.23 mg/dL and 86.6 ± 10.3 mL/min in the erythropoietin group and 1.31 ± 0.35 mg/dL and 79.7 ± 12.5 mL/min in the control group, respectively (P = .04 and P = .02). None of the patients lost their grafts and no death was reported. There were no adverse effects in the erythropoietin group. CONCLUSIONS: Our findings suggest that erythropoietin may have beneficial effects on graft function if administered early after transplantation. Erythropoietin can be used for all kidney transplant recipients for protecting the allograft due to its effects on tissue oxygenation.

Two decades of experience in mucormycosis after kidney transplantation.

BACKGROUND: Invasive mucormycosis is a very rare infection after kidney transplantation. Here, we report 25 renal transplant recipients with mucormycosis; to our knowledge, this is the largest reported population of mucormycosis in these patients. MATERIAL/METHODS: In a retrospective study, we collected all kidney transplants with mucormycosis from 9 Transplant Centers of Iran from 1990 to 2010. The definitive diagnosis of mucormycosis was established by obtaining a biopsy specimen of the involved tissue. RESULTS: The most form of disease was rhino-cerebral (n =13), followed by pulmonary (n=7). Overall mortality rate was 52% (n=13), particularly in recipients with pulmonary infection (100%); however, the mortality rate in rhino-cerebral form of disease was low (30.8%). There was no statistically significant difference in mortality rate between male and female (P=0.8). In addition, no significant differences were seen in mortality rate with age of patients (p=0.8) and time of diagnosis since transplantation (p=0.3). Pulmonary infection was more seen in recipients received azathioprine compared to those on mycophenolate mofetil (p=0.006). CONCLUSIONS: Mucormycosis after renal transplantation has a poor prognosis, particularly patients with pulmonary involvement.

Role of folic acid in atherosclerosis after kidney transplant: a double-blind, randomized, placebo-controlled clinical trial.

OBJECTIVES: We investigated the effects of folic acid supplementation on plasma total homocysteine levels and carotid intima-media thickness after kidney transplant. MATERIALS AND METHODS: Sixty patients who had undergone a kidney transplant were studied in this double-blind, randomized, placebo-controlled clinical trial. Those subjects were randomized to receive either 5 mg/d of oral folic acid or an equivalent dosage of placebo. The main outcome variables were the plasma total homocysteine level and carotid intima-media thickness (determined via B-mode sonography) at baseline and 2, 4, and 6 months after kidney transplant. We used independent and paired sample t tests for data analysis. RESULTS: The mean age of the patients was 40.9 -/+ 10 years, and 32 of those subjects (58.2%) were men. In the control group, the plasma total homocysteine levels were 19 micromol/L at baseline, 18.7 micromol/L after 2 months, 19.3 micromol/L after 4 months, and 20 micromol/L after 6 months; and the carotid intima-media thickness measurements were 0.81 mm at baseline, 0.82 mm after 2 months, 0.84 mm after 4 months, and 0.85 mm after 6 months. In the folic acid group, the plasma total homocysteine levels were 18.5 micromol/L at baseline, 4.7 micromol/L after 2 months, 12.9 micromol/L after 4 months, and 10.9 micromol/L after 6 months; and the carotid intima-media thickness measurements were 0.73 mm at baseline, 0.73 mm after 2 months, 0.72 mm after 4 months, and 0.71 mm after 6 months. CONCLUSIONS: Folic acid supplementation reduces both the plasma total homocysteine level and carotid intima-media thickness shortly after kidney transplant.

Does CMV infection increase the incidence of infective endocarditis following kidney transplantation?

BACKGROUND: Infective endocarditis (IE) is a rare but life threatening infection after renal transplantation. In addition, coinfection of CMV and IE has not been reported. Therefore, the current study was initiated to determine whether CMV infection is a risk factor for developing of IE after kidney transplantation. MATERIAL/METHODS: In a retrospectively study, we analyzed the medical records of 3700 kidney recipients at two transplant centers in Iran, between January 2000 and June 2008 for infective endocarditis. RESULTS: During the study, 15 patients with IE hospitalized in our centers were included. The predominant causative microorganisms (60%) were group D non-enterococcal streptococci and enterococci. Patient survival rate in all recipients was 66% at 6 months. Data analysis showed no significant differences in 6 months patient survival from hospitalization between both groups with and without CMV infection (P=0.2). The presentation time of infective endocarditis in recipients with CMV coinfection was more likely to be early when compared to CMV negative coinfection patients (P=0.03). CONCLUSIONS: The present study indicates that CMV infection may lead to predispose to infective endocarditis after kidney transplantation. Rapid diagnosis, effective treatment, and prompt recognition of complications in kidney transplant recipients are essential to good patient outcome.

Pre-transplant and post-transplant soluble CD30 for prediction and diagnosis of acute kidney allograft rejection.

BACKGROUND: Serum levels of soluble CD30 (sCD30) have been considered as a predictor of acute kidney allograft rejection. We have evaluated the pre-transplant and post-transplant levels of sCD30 with the aim of determining its value in predicting and diagnosing kidney rejection. METHODS: We measured sCD30 serum levels before kidney transplantation, 5 days post-operatively, and at creatinine elevation episodes. The predictive value of sCD30 for diagnosing acute rejection (AR) within the first 6 post-operative months was assessed in 203 kidney recipients from living donors. RESULTS: Pre-transplant and post-operative levels of serum sCD30 were 58.10 +/- 52.55 and 51.55 +/- 49.65 U/ml, respectively (P = 0.12). Twenty-three patients experienced biopsy-proven acute rejection, and 28 had acute allograft dysfunction due to non-immunologic diseases. The pre-transplant sCD30 level was not different between patients with and without AR. However, post-transplant sCD30 was higher in the AR group. The median serum level of post-transplant sCD30 was 52 U/ml in the AR group and 26.3 U/ml in a control group (P < 0.001). The relative changes of sCD30 on day 5 were higher in patients with AR (P = 0.003). Based on post-transplant sCD30 levels, we were able to differentiate between kidney recipients who experienced an AR within 6 months post-surgery and those without an AR (cutoff value 41 U/ml; sensitivity 70%; specificity 71.7%). The level of sCD30 during periods of elevated serum creatinine was not independently associated with the diagnosis of AR. CONCLUSION: Post-transplant sCD30 levels and their relative changes are higher in patients experiencing AR. We propose further studies on the post-transplant trend of this marker for the prediction of AR.

Kaposi's sarcoma following living donor kidney transplantation: review of 7,939 recipients.

INTRODUCTION: Kaposi's sarcoma (KS) is one of the most common tumors to occur in kidney recipients, especially in the Middle East countries. Limited data with adequate sample size exist about the development of KS in living kidney recipients. METHODS: Therefore, we made a plan for a multicenter study, accounting for up to 36% (n = 7,939) of all kidney transplantation in Iran, to determine the incidence of KS after kidney transplantation between 1984 and 2007. RESULTS: Fifty-five (0.69%) recipients who developed KS after kidney transplantation were retrospectively evaluated with a median follow-up of 24 (1-180) months. KS occurred more often in older age when compared to patients without KS (49 +/- 12 vs. 38 +/- 15 years, P = 0.000). KS was frequently found during the first 2 years after transplantation (72.7%). Skin involvement was universal. Furthermore, overall mortality rate was 18%, and it was higher in patients with visceral involvement compared to those with mucocutaneous lesions (P = 0.01). However, KS had no adverse affect on patient and graft survival rates compared to those without KS. Forty-four patients with limited mucocutaneous disease and four with visceral disease responded to withdrawal or reduction of immunosuppression with or without other treatment modalities. Renal function was preserved when immunosuppression was reduced instead of withdrawn in patients with and without visceral involvement (P = 0.001 and 0.008, respectively). CONCLUSION: The high incidence of KS in this large population studied, as compared to that reported in other transplant patient groups, suggests that genetic predisposition may play a pathogenetic role.

Invasive fungal infections following renal transplantation: a review of 2410 recipients.

BACKGROUND: Organ transplant recipients, on long-term graft preserving immunosuppressive therapy, are at increased risk for life threatening opportunistic fungal infections. MATERIAL/METHODS: In order to evaluate the incidence of invasive fungal infections (IFIs) and to identify the most common fungal pathogens, we conducted a retrospective study on 2410 ESRD cases undergone living kidney transplantation in three transplant centers between 1998 and 2008. RESULTS: IFIs developed in 21 recipients (0.87%), 17 male and 4 female. Their immunosuppression was cyclosporine based. The mean age of patients was 48+/-10 (ranged from 32 to 67) years. Diagnosis was made by radiological findings, positive blood or bronchoalveolar lavage (BAL) cultures and tissue biopsies. Mucormycosis was the most common cause of IFIs in population studied (n=11), followed by disseminated candidiasis (n=4), aspergillosis (n=3), nocardiasis (n=2) and histoplasmosis (n=1). Pulmonary involvement was dominant (47.6%). The treatment was successful in only 10 patients and the rest died. CONCLUSIONS: In our large series of kidney transplant recipients, mucormycosis was found to be the most common cause of invasive fungal infection. Prompt diagnosis and treatment are necessary to avoid the life threatening complications and may greatly improve prognosis.

Spirometry parameters in patients undergoing hemodialysis with bicarbonate and acetate dialysates.

INTRODUCTION: End-stage renal disease causes impairment of all body organs including the heart and the lung. The main problems in the afflicted patients are pulmonary edema due to increased permeability of the capillaries, intravascular and interstitial volume overload, hypertension, and congestive heart failure. These changes cause altered physiologic and mechanical function of the lungs and subsequently increase in airway resistance. We aimed to study the impact of hemodialysis on spirometry parameters. MATERIALS AND METHODS: In a cross-sectional study performed on 41 patients on maintenance hemodialysis, spirometry was done before and after the dialysis session. The patients were on either acetate or bicarbonate hemodialysis with the same method, dialysis machine, and duration of dialysis. Alterations in spirometry parameters including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and maximal midexpiratory flow rate were determined and their relation with serum electrolytes, serum creatinine, blood urea nitrogen, and hemoglobin were analyzed. RESULTS: Twenty-nine patients undergoing dialysis with bicarbonate dialysate and 21 on dialysis with acetate were compared. Improvement in spirometry parameters was only significant in patients undergoing dialysis with bicarbonate dialysate. All spirometry parameters showed significant increases in the bicarbonate group except for the FEV1/FVC ratio. Furthermore, significant increase in these parameters was only prominent in the men. Postdialysis weight reduction and laboratory indexes had no significant correlation with improvement of spirometry parameters. CONCLUSIONS: Dialysis with bicarbonate dialysate causes significant improvement in spirometry parameters in men on maintenance dialysis. This effect might be independent of the effect of removing the volume overload by dialysis.