Could the CCR5-Delta32 mutation be protective in SARS-CoV-2 infection?

Increasing evidence points to host genetics as a factor in COVID-19 prevalence and outcome. CCR5 is a receptor for proinflammatory chemokines that are involved in host responses, especially to viruses. The CCR5-delta32 minor allele is an interesting variant, given the role of CCR5 in some viral infections, particularly HIV-1. Recent studies of the impact of CCR5-delta32 on COVID-19 risk and severity have yielded contradictory results. This ecologic study shows that the CCR5-delta32 allelic frequency in a European population was significantly negatively correlated with the number of COVID-19 cases (p=0.035) and deaths (p=0.006) during the second pandemic wave. These results suggest that CCR5-delta32 may be protective against SARS-CoV-2 infection, as it is against HIV infection, and could be predictive of COVID-19 risk and severity. Further studies based on samples from populations of different genetic backgrounds are needed to validate these statistically obtained findings.

Protective effects of whey on rat liver damage induced by chronic alcohol intake.

In 2012, alcohol liver disease resulted in 3.3 million-5.9% of global deaths. This study introduced whey protection capacity against chronic alcohol-induced liver injury. Rats were orally administered to 12% ethanol solution in water (ad libitum, average 8.14 g of ethanol/kg body weight (b.w.)/day) alone or combined with whey ( per os, 2 g/kg b.w./day). After 6-week treatment, chronic ethanol consumption induced significant histopathological liver changes: congestion, central vein dilation, hepatic portal vein branch dilation, Kupffer cells hyperplasia, fatty liver changes, and hepatocytes focal necrosis. Ethanol significantly increased liver catalase activity and glutathione reductase protein expression without significant effects on antioxidative enzymes: glutathione peroxidase (GPx), copper-zinc-containing superoxide dismutase (CuZnSOD) and manganese-containing superoxide dismutase (MnSOD). Co-treatment with whey significantly attenuated pathohistological changes induced by ethanol ingestion and increased GSH-Px and nuclear factor kappa B (NF-κB) protein expression. Our results showed positive effects of whey on liver chronically exposed to ethanol, which seem to be associated with NF-κB-GPx signaling.

Toxicity study of DE-EDCP as a potential drug for cancer therapy: Toxicity profile of DE-EDCP.

It was reported that novel O, O'-diethyl-(S, S)-ethylenediamine- N, N'-di-2-(3-cyclohexyl) propanoate dihydrochloride (DE-EDCP) displayed in vitro antiproliferative activity on several human and mouse cancer cell lines, which was comparable to that of the prototypical anticancer drug cisplatin. In order to reveal its toxicity profile, acute and repeated-dose toxicity studies were performed in Naval Medical Research Institute (NMRI) Han mice. The intravenous LD50 values of DE-EDCP were found to be 95.3 and 101.3 mg/kg body weight in female and male mice, respectively. In the subacute toxicity study, DE-EDCP was administered intravenously at the doses of 15, 25, and 40 mg/kg/day for a period of 28 days. There were no adverse effects on general condition, growth, feed and water consumption, and hematological parameters. There was a significant increase in urea and alanine aminotransferase in female mice and aspartate aminotransferase and alkaline phosphatase in both genders in 40 mg/kg/day dose-treated group. The histopathological changes confined to the liver and kidney, but in other organs were not found. Satellite group revealed that changes in the kidney and liver were less pronounced, suggesting their reversibility. Interactions with DNA could also be of importance for understanding DE-EDCP toxic side effects. Hyperchromic effect obtained with ultraviolet-visible, suggested electrostatic interactions between DE-EDCP and calf thymus DNA. The toxicity testing of DE-EDCP was conducted to predict human outcomes.

VITAMIN D STATUS IN PATIENTS WITH MENTAL DISORDERS: A CROSS-SECTIONAL ANALYSIS OF SINGLE COHORT FROM ROUTINE PRACTICE.

CONTEXT: Clinical research suggests that vitamin D deficiency correlates with mental illnesses. OBJECTIVE: The aim was to prove that the patients from the psychiatric health care service in Serbia had higher vitamin D deficiency than patients from general practice. DESIGN: The study had a cross-sectional design. METHODS: The study included 47 patients aged 19 - 76 of both sexes with different mental disorders. We performed sample size calculation on available data for vitamin D deficiency in patients in health care facilities compared with the general population. The concentrations of vitamin D in serums were measured by HPLC (high performance/pressure liquid chromatography). RESULTS: The mean value of vitamin D (standard deviation) in the whole group of study subjects was 16.27(10.62) ng/mL; 68.1% of the patients had a deficiency of vitamin D (25(OH)D<20 ng/mL). The difference is statistically significant from expected proportion of people with vitamin D deficiency in general practice (p=0.040). Serum concentrations of 25(OH)D were significantly correlated with serum concentrations of phosphorus (ϱ=0.336, p=0.024) and sodium (ϱ=0.304, p=0.038). CONCLUSIONS: The patients of psychiatry health care had significantly higher frequency of vitamin D deficiency than expected. There is a significant association between serum levels of vitamin D, and phosphate and sodium.

Kidney length in healthy members of Balkan endemic nephropathy families.

BACKGROUND: Kidney size may differ between healthy members of Balkan endemic nephropathy (BEN) and non-BEN families. The present study was designed to elucidate this, in comparison with values for BEN patients. METHODS: A total of 71 BEN patients (34 males, 64.4 ± 12.0 years), 74 healthy BEN family members (39 males, 49.1 ± 12.2 years), and 59 non-BEN family members (19 males, 49.2 ± 12.3 years) were involved. We measured the longest craniocaudal length and minimal parenchymal thickness on each kidney of all examined subjects using ultrasound. RESULTS: No significant difference was found between the kidney length of healthy subjects from BEN (11.0 ± 0.8 cm) and non-BEN families (10.9 ± 0.8 cm), but kidneys were significantly longer than in BEN patients (9.9 ± 1.3 cm). Minimal parenchymal thickness was similar in all three groups. When subjects from each group were divided according to estimated glomerular filtration rate (eGFR), kidney length of the healthy groups was significantly longer than in BEN patients both in stage 1 (p =0.039) and stage 2 (p =0.044) of chronic kidney disease. The parental history of BEN was not associated with kidney dimensions, eGFR, or urinary excretion of albumin and alpha1-microglobulin. CONCLUSION: Kidneys of BEN patients were significantly shorter than in healthy members of both BEN and non-BEN families, but no difference was found in kidney length and parenchymal thickness between healthy members of BEN and non-BEN families. No significant association was found between parental history of BEN and kidney size and function either in BEN patients or in healthy members from BEN families. Hippokratia 2015; 19 (4): 304-308.

Characterisation and preliminary lipid-lowering evaluation of Lactobacillus isolated from a traditional Serbian dairy product.

We investigated the potential probiotic properties of indigenous lactic acid bacteria (LAB) isolated from Serbian homemade cheese. Seventeen LAB strains were isolated and characterised using standard protocols. One of the strains showed several probiotic properties: survival at low pH and in bile salts solution, antimicrobial activity, susceptibility to antibiotics and adhesion to hexodecane. DNA analysis identified the isolate as Lactobacillus casei, hereafter named L. casei 5s. The lipid lowering effect of L. casei 5s was evaluated in vivo using a hyperlipidemic rat model. Orally administered L. casei 5s significantly decreased the elevated total serum cholesterol and triglycerides, and attenuated macro vesicular steatosis in the liver. Moreover, L. casei 5s improved the intestinal microbial balance in favour of lactobacilli, while decreasing the number of Escherichia coli cells. The bacteria were re-isolated and identified from the surface of the intestinal mucosa and from the faecal samples of treated animals, indicating adhesiveness and colonisation ability. The results of an acute oral toxicity study in mice and the absence of translocation to other organs demonstrated the safety of the strain. In conclusion, L. casei 5s demonstrated promising probiotic potential and might be a good candidate for more detailed investigations.

Potential influence of tubular dysfunction on the difference between estimated and measured glomerular filtration rate after kidney transplantation.

PURPOSE: Because no consensus exists regarding the most accurate calculation to estimate glomerular filtration rate (GFR) based on serum creatinine concentrations (sCr) after kidney transplantation, this study sought to assess the potential role of tubular dysfunction on GFR estimates using various equations as well as the effect of pharmacologic blockades on tubular secretion of creatinine on creatinine clearance (ClCr). METHODS: Iohexol GFR (mGFR) was performed in 17 stable kidney transplant recipients(R) at >24 months post-transplantation. Their mean age was 48.3 ± 11.3 years. All R were treated with a calcineurin inhibitor (CNI). At the time of study we measured sCr, 24 hour-ClCr, cystatin C, 24-hour proteinuria, microalbuminuria, FE Na, alfa1-microglobulinuria (alfa1-MG), and CNI concentrations. To block tubular secretion of Cr, recipients were prescribed cimetidine (2400 mg) 2 days before the sCr measurement. Additionally, to exclude dietary influences on sCr, R did not eat meat for 2 days before testing. GFR was estimated using the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Cockroft-Gault (C&G), and Cystatin C (Cyst C) GFR equations. Mean kidney graft function over the previous 6 months was used as the control. Pearson correlation was determined between the differences between mGFR and estimatedGFR: Iohexol minus MDRD, EPI, Cyst C or C&G GFR for paired estimates. The diagnostic accuracy of the eGFRs to detect an mGFR of 60 mL/min/1.73 m(2) was examined by receiver operating characteristic curves. RESULTS: Mean mGFR was 75.2 ± 35.8 mL/min/1.73 m(2). The sCr increased but the 24-hour ClCr, MDRD, EPI, and C&G decreased after vs before cimetidine. The difference was significant for sCr (F = 12.933; P = .002) and MDRD GFR (F = 15.750; P = .001). mGFR was not significantly higher than all pair values of eGFRs, and not significantly lower than 24-hour ClCr before and after cimetidine. However, in comparison to all eGFRs, ClCr after cimetidine most approached mGFR. A significant positive correlation was observed between alfa1-MG and the difference between mGFR and MDRD (before, r = .543 [P = .045]; after cimetidine, 0.568 [P = .034]), EPI (before, r = 0.516 [P = .050]; after cimetidine, r = 0.562 [P = .036]), and ClCr (r = 0.633; P = .016), C&G (P = .581; P = .029) before cimetidine. Accuracy of eGFRs to detect mGFR of 60 mL/min/1.73 m(2) showed EPI GFR before cimetidine to show diagnostic accuracy for patients with GFR >60 mL/min/1.73 m(2) with a sensitivity of 81.8% and a specificity of 71.4%. CONCLUSIONS: Because mGFR is unavailable in many transplant centers, determination of ClCr after cimetidine may help to achieve a more accurate diagnosis of CKD among transplant patients.

Malignant biliary stenosis treated with two percutaneous stents--case report.

INTRODUCTION: During last three decades interventional radiology became most powerfull tool in palliative treatment of patients with malignant biliary stenosis. CASE REPORT: We report a case of 62-year-old patient with malignant biliary obstruction caused by recidivant tumor of common bile duct remnant with infiltration of previously created hepaticojejunostomia. Biliary decompression was achieved by placement of two self-expanding metallic stents. DISCUSSION: In presented patient, due to previous surgery percutaneous approach was mandatory. Also, considering the unresectability of recidivant lesion and poor prognosis, definitive, preferable internal biliary drainage was to be achieved. Therefore the placement of metallic self-expanding stent was the therapeutic method of choice. CONCLUSION: The aim of percutaneous minimally invasive radiological interventions is to achieve effective biliary decompression with internal bile drainage if possible.

CTLA-4 +49 A/G gene polymorphism in Croatian and Slovenian multiple sclerosis patients.

Polymorphisms in the CTLA-4 gene are known to be important in several autoimmune diseases, including multiple sclerosis (MS). Previous studies on the impact of CTLA-4 +49 A/G gene polymorphism have given contradictory results. We investigated the possible influence of this polymorphism on MS susceptibility and disease behaviour in Croatian and Slovenian populations. Genotyping was performed in 367 patients with MS and 480 control subjects using PCR-RFLP method. The G allele was present in 216 (58.9%) patients with MS vs. 282 (58.7%) healthy controls (P = 0.975, OR = 1.01, 95% CI = 0.76-1.32). No significant differences were observed in CTLA-4 +49 A or G allele distribution between patients and controls, indicating that this polymorphism does not influence susceptibility to MS in the surveyed populations. No correlation was observed between G allele carrier status and age at disease onset, disease course or severity.

A case of lichen ruber planus in a patient with familial multiple sclerosis.

Multiple sclerosis and lichen ruber planus are clinically and histologically distinct complex disorders of putative autoimmune aetiology that are fairly commonly observed in isolation but rarely found in combination. Only two previous reports have described lichen skin disorders in association with multiple sclerosis. The present report describes the case of a 51-year-old Caucasian woman exhibiting both familial multiple sclerosis and lichen ruber planus. This combination may have occurred by chance or it might imply that these disorders share common mechanisms in their pathogenesis.

Molecular response to imatinib in patient with Ph negative p190 BCR-ABL transcript positive chronic myeloid leukemia with cyclic leukocytosis.

An atypical case of Philadelphia (Ph) negative, e1a2 BCR-ABL transcript positive chronic myeloid leukemia (CML) characterized with cyclic periodic leukocytosis and spontaneous remissions is reported. The patient was treated with imatinib and good hematology response with molecular remission was achieved. So far, only few Ph positive CML patients expressing p190 BCR-ABL protein and different clinical characteristics and treatment have been described in the literature. This is the first report of Philadelphia negative, p190 BCR-ABL positive CML with cyclic spontaneous oscillation of white blood cell count (WBC), and excellent response to imatinib treatment.

Management of painful spinal lesions caused by multiple myeloma using percutaneous acrylic cement injection.

BACKGROUND AND PURPOSE: Spinal lesions with marked destruction are common site of morbidity in patients with multiple myeloma causing serious clinical symptoms. The aim of the study was to evaluate the therapeutic benefit of percutaneous vertebroplasty (PVP) in treating vertebral body lesions in patients suffering from multiple myeloma. MATERIALS AND METHODS: Twenty nine patients (55 vertebral bodies) were treated after complete diagnostic evaluation, preparation and obtaining informed consent. Needle position and acrylic material injection was performed under fluoroscopic guidance. RESULTS: Average visual analogue score dropped from 7.8 before to 2.3 after the intervention. Soft tissue leak was present at 9 treated levels, small epidural cement collection at 5, venous leak at 4 and intradiscal leak at 3 levels without any clinically manifest complications. The effects of PVP were stable in all of the patients at 12 months follow-up. Subjective outcome scores collected through follow-up showed improvement of +1.45 in pain, + 1.15 in ambulation and + 1.23 in medication use. There were recurrence of back pain in 9 patients at non-treated levels due to the new lesions. CONCLUSION: In our series, PVP of painful lesions caused by multiple myeloma provides immediate and long-term pain relief. The procedure is safe and, despite of the present leakage of cement, may be performed on outpatients basis.

Molecular characteristics and prognostic significance of Bcl-2/IgH gene rearrangement in Serbian follicular lymphoma patients.

Follicular lymphoma (FL) is characterized by the presence of a t(14;18) chromosomal translocation that results in overexpression of bcl-2 protein. Bcl-2/IgH gene rearrangement is detected in 80-90% of follicular lymphomas in Western countries. The aim of this study was to analyze the bcl-2/IgH rearrangement in FL lymphoma patients in Serbia, by PCR technique, correlate molecular findings with clinical characteristics and outcome and assess the prognostic significance of these rearrangements. One hundred-seven patients (median age, 54 years; male/female ratio:60/47) diagnosed with FL were included in the study. DNA samples were obtained from paraffin embedded lymphoid tissue of patients. Bcl-2/IgH rearrangement was assessed for the major breakpoint region (MBR), 5' MBR and the minor cluster region (mcr) breakpoints by PCR technique. We detected a t(14;18) in 81.3% (87/107) of patients. The distribution of bcl-2-IgH rearrangement was as follows: 88,5% (77/87) in MBR breakpoint, 10,35% (9/87) in 5' MBR, whereas mcr bcl-2-IgH rearrangement was observed in one patient (1.15%). No rearrangements were detected in remaining 20 patients (18.7%). This is the first analyses of the frequency of the bcl-2/IgH gene rearrangement in Serbian FL patients, as well as in Eastern European countries. There was no correlation between presence of bcl-2/IgH gene rearrangement and clinical outcome of disease. Incidence of bcl-2/IgH gene rearrangement in Serbian FL patients is relatively high, and similar to frequency in Western countries. Presence of this rearrangement in tumor tissue is not of prognostic significance.

Nateglinide or gliclazide in combination with metformin for treatment of patients with type 2 diabetes mellitus inadequately controlled on maximum doses of metformin alone: 1-year trial results.

AIM: To compare long-term efficacy and safety of nateglinide plus metformin with those of gliclazide plus metformin in patients with type 2 diabetes not adequately controlled with metformin monotherapy. METHODS: Double-blind, double-dummy, multicentre study extended to a total of 52 weeks. Patients with inadequate glucose control on maximal doses of metformin were randomized to nateglinide (N = 133) or gliclazide (N = 129) add-on treatment. After the initial 6-month study, the majority of patients in the nateglinide group [n = 112 (93.3%)] and in the gliclazide group [n = 101 (92.7%)] entered a 6-month, double-blind, extension study. RESULTS: There was no significant difference between treatment regimens in haemoglobin Alc (HbA1c) change from baseline to 52 weeks (-0.14% for nateglinide vs. -0.27% for gliclazide; p = 0.396). Proportions of patients achieving an endpoint HbA1c of <7% were similar (40 vs. 47.4%) for nateglinide and gliclazide groups. There was no significant between-treatment difference in fasting plasma glucose change from baseline to 52 weeks (nateglinide: -0.2 mmol/l and gliclazide: -0.7 mmol/l; p = 0.096). The decreases in prandial plasma glucose area under the curve(0-4 h) from baseline were -3.26 and -1.86 h x mmol/l in the nateglinide and the gliclazide groups respectively, and the change was statistically significant in the nateglinide group only (p = 0.006). Initial insulin response to a meal was augmented with nateglinide treatment only, without between-treatment difference in 2-h insulin response. The overall rate of hypoglycaemic events was similar with nateglinide and gliclazide combinations with metformin. Nateglinide plus metformin treatment was not associated with weight gain. CONCLUSIONS: No significant difference was seen between nateglinide plus metformin and gliclazide plus metformin in terms of HbA1c. Treatment with nateglinide plus metformin for up to 12 months was not associated with weight gain.

Angiotensin-converting enzyme I/D gene polymorphism and risk of multiple sclerosis.

OBJECTIVES: Angiotensin-converting enzyme (ACE) activity is increased in blood and cerebrospinal fluid of patients with multiple sclerosis (MS). In addition, in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, the blockade of ACE suppresses the disease itself. To analyze the genetic association of the ACE gene with MS, we examined ACE gene insertion/deletion (I/D) polymorphism in MS patients. MATERIALS AND METHODS: A total of 313 MS patients from Slovenia and Croatia and 376 healthy controls were genotyped by polymerase chain reaction method. RESULTS: We found statistically significant differences in the distribution of ACE I/D allele frequencies (P < 0.01) and genotypes (P < 0.04) in male patients. ACE DD genotype was associated with MS in men at an odds ratio of 1.86 (95% CI 1.09-3.19, P = 0.02). CONCLUSIONS: DD genotype of ACE gene might contribute to a higher risk of developing MS in men.

Comparison of nateglinide and gliclazide in combination with metformin, for treatment of patients with Type 2 diabetes mellitus inadequately controlled on maximum doses of metformin alone.

AIM: To compare the effects of nateglinide plus metformin with gliclazide plus metformin on glycaemic control in patients with Type 2 diabetes. METHODS: Double-blind, double-dummy, parallel group, randomized, multicentre study over 24 weeks. Patients with inadequate glucose control on maximal doses of metformin were randomized to additionally receive nateglinide (n = 133) or gliclazide (n = 129). Changes from baseline in HbA1c, fasting plasma glucose (FPG) and mealtime glucose and insulin excursions were examined. RESULTS: HbA1c was significantly (P < 0.001) decreased from baseline in both treatment groups (mean changes: nateglinide -0.41%, gliclazide -0.57%), but with no significant difference between treatments. Proportions of patients achieving a reduction of HbA1c >or= 0.5% or an end point HbA1c < 7% were also similar (nateglinide 58.1%, gliclazide 60.2%). Changes from baseline in FPG were similarly significant in both treatment groups (nateglinide -0.63, gliclazide -0.82 mmol/l). Reduction from baseline in maximum postprandial glucose excursion were significant in the nateglinide group only (nateglinide -0.71, gliclazide -0.10 mmol/l; P = 0.037 for difference). Postprandial insulin levels were significantly higher with nateglinide compared with gliclazide. The overall rate of hypoglycaemia events was similar in the nateglinide group compared with the gliclazide group. CONCLUSIONS: No significant difference was seen between nateglinide plus metformin and gliclazide plus metformin in terms of HbA1c. However, the nateglinide combination demonstrated better postprandial glucose control.

Predictive value of prognostic indices in patients with follicular lymphomas.

PURPOSE: The aim of this study was to compare which of three indices--International Prognostic Index (IPI), Italian Lymphoma Intergroup (ILI) index, Follicular Lymphoma adapted International Prognostic Index (FLIPI)--is the most useful in predicting outcome in follicular lymphoma (FL) patients and to identify other clinical and laboratory prognostic factors that influence survival. PATIENTS AND METHODS: Clinical and prognostic studies were carried out in 99 patients with FL. RESULTS: The distribution of patients in IPI risk groups was 44.4%, 19.2%, and 36.4% of cases classified as low, intermediate, and high risk. According to ILI, low-, intermediate-, and high-risk scores were present in 34.3%; 27.3%, and 38.4% of FL patients. After applying the FLIPI index, the patients were divided into three risk groups: low (21.2% of cases), intermediate (39.4%), and high (39.4%) of FL patients. Survival curves demonstrated a high significant difference for the low- and high-risk group according to IPI and FLIPI (log rank=91.13 and 82.17 respectively; p < 0.0001). Difference in overall survival (OS) and failure-free survival (FFS) among low-, intermediate-, and high-risk groups according to ILI was statistically significant (log rank test p < 0.0001). CONCLUSION: All three indices are important tools for prognostic evaluation of FL patients, as well as useful in identifying FL patients with poor outcome. IPI and FLIPI classify patients into two risk groups (low/intermediate- and high-risk groups) with significance difference in OS and FFS, but ILI is more reliable in stratifying patients in low-, intermediate-, and high-risk groups.

Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response.

OBJECTIVE: A novel treatment option for diabetic patients is the enhancement of incretin hormone activity by inhibition of the enzyme dipeptidyl peptidase-4 (DPP-4). This study was designed to establish a dose of the DPP-4-inhibitor vildagliptin (LAF237) that was effective in reducing HbA1c levels and was safe and well tolerated in patients with type 2 diabetes. PATIENTS AND METHODS: The study of 279 patients with type 2 diabetes consisted of a 4-week run-in phase where patients received placebo and a 12-week active treatment phase where they received one of the following dosages of vildagliptin: 25 mg twice daily, 25, 50 or 100 mg once daily (qd), or placebo. RESULTS: There was a statistically significant reduction in HbA1c levels in the vildagliptin 50 mg qd (p=0.003) and 100 mg qd groups (p=0.004) compared with the placebo group. The mean 4-h postprandial glucose level was significantly reduced from placebo in the vildagliptin 50 mg qd group (p = 0.012) and mean 4-h postprandial insulin was significantly increased from baseline vs. placebo in the vildagliptin 100 mg qd group (p=0.022). The assessment of beta-cell function (HOMA-B) was significantly increased in the vildagliptin 100 mg qd treatment group (p=0.007). The incidence of adverse events was similar in all treatment groups including placebo. CONCLUSIONS: Vildagliptin, at 50 and 100 mg qd, was effective in reducing HbA1c levels compared with placebo in patients with type 2 diabetes. Vildagliptin at dosages up to 100 mg qd appeared safe and well tolerated.

Conversion of azathioprine to mycophenolate mofetil and chronic graft failure progression.

The purpose of the study was to evaluate the impact of conversion from azathioprine (AZA) to mycophenolate mofetil (MMF) on graft function in 35 renal transplant recipients with chronic allograft nephropathy (CAN). The immunosuppressive regimen originally consisted of AZA, cyclosporine (CsA), and prednisone (Pr). At the onset of the study (mean period = 39 posttransplant months), a graft biopsy was performed on all patients who were randomly divided into group 1 (n = 17) in whom MMF was introduced instead of AZA. The remaining 18 subjects (group 2) were maintained on the previous regimen. Two periods were analyzed: period I: 12 months before, and period II: 12 months after biopsy and therapy conversion. Graft function was assessed monthly by measurements of the 24-hour creatinine clearance (CCr). Analysis of variance (ANOVA) was used to compare the differences in CCr and proteinuria between the two groups. No difference was observed in the baseline characteristics, in the incidence of delayed graft function and acute rejection, or in the mean CsA dose. Pathohistological analysis revealed advanced CAN in the majority of patients in both groups. The morphological changes negatively correlated with graft function. The graft function showed parallel deterioration in the two groups; no significant difference was observed in the mean CCr values in the periods studied. Proteinuria was similar for both groups throughout the study. Conversion of AZA to MMF in recipients with CAN, albeit safe, was without significant benefit on the progression of chronic graft failure over the period of a year.