Longitudinal non-targeted metabolomic profiling of urine samples for monitoring of kidney transplantation patients.

The assessment of kidney function within the first year following transplantation is crucial for predicting long-term graft survival. This study aimed to develop a robust and accurate model using metabolite profiles to predict early long-term outcomes in patient groups at the highest risk of early graft loss. A group of 61 kidney transplant recipients underwent thorough monitoring during a one-year follow-up period, which included a one-week hospital stay and follow-up assessments at three and six months. Based on their 12-month follow-up serum creatinine levels: Group 2 had levels exceeding 1.5 mg/dl, while Group 1 had levels below 1.5 mg/dl. Metabolites were detected by mass spectrometer and first pre-processed. Univariate and multivariate statistical analyses were employed to identify significant differences between the two groups. Nineteen metabolites were found to differ significantly in the 1st week, and seventeen metabolites in the 3rd month (adjusted p-value < 0.05, quality control (QC) < 30, a fold change (FC) > 1.1 or a FC < 0.91, Variable Influence on Projection (VIP) > 1). However, no significant differences were observed in the 6th month. These distinctive metabolites mainly belonged to lipid, fatty acid, and amino acid categories. Ten models were constructed using a backward conditional approach, with the best performance seen in model 5 for Group 2 at the 1st-week mark (AUC 0.900) and model 3 at the 3rd-month mark (AUC 0.924). In conclusion, the models developed in the early stages may offer potential benefits in the management of kidney transplant patients.

The effect of histopathologic and clinical features on allograft survival in renal transplant patients with antibody-mediated rejection.

BACKGROUND: Antibody-mediated rejection is a frequent cause of graft failure; however, prognostic indications of this complication have not been well defined. The aim of this study was to evaluate the association of histopathological and clinical features and to determine the effect of these findings on allograft survival in patients with AMR. METHODS: Fifty-two patients suffered from AMR (30 male; mean age 39 ± 11 years) were included in the study. Data were investigated retrospectively and graft survival was analyzed. All transplant biopsies were evaluated according to Banff 2009 classification. RESULTS: Of the 52 cases, 45 were transplanted from living-donors. Twenty-one patients were diagnosed in the first 3-months after transplantation. Graft survival was 65% at 12 months and 54% at 36 months. Mean serum creatinine at time of biopsy was 3.8 ± 3.6 mg/dL. Thirty-five of the 52 cases showed diffuse C4d positivity, 12 cases showed focal and 5 remained C4d negative. One of the patients died, 13 experienced graft loss and 38 survived with functioning grafts. Serum creatinine levels at time of biopsy were correlated with graft survival (p = .021: OR = 1.10: 95 % CI = 1.015-1.199). In terms of the impact of pathological findings; tubulitis (p=.007: OR = 2.62: 95 % CI = 1.301-5.276), intimal arteritis (p=.017: OR = 2.85: 95% CI = 1.205-6.744) and interstitial infiltration (p=.004: OR = 3.37: 95% CI = 1.465-7.752) were associated with graft survival. CONCLUSIONS: Serum creatinine at time of biopsy, tubulitis, intimal arteritis and interstitial infiltration were significantly associated with graft survival. Antibody-mediated rejection is associated with reduced long-term graft survival.

Sirolimus-Induced Diffuse Alveolar Hemorrhage: A Case Report.

Sirolimus is a mammalian target of the rapamycin, a protein kinase, which is responsible for inhibition of T cell and B cell proliferation. Sirolimus has side effects on lugs, and may cause cryptogenic organizing pneumonia, diffuse alveolar hemorrhage, lymphocytic pneumonitis, hypersensitivity pneumonitis, desquamative interstitial pneumonia, and pulmonary alveolar proteinosis. Diagnosis is based on the combination of clinical, radiological, histological, and pathological investigation. We report a case of diffuse alveolar hemorrhage in a 33-year-old, female renal transplant recipient. After discontinuation of sirolimus, radiological images and clinical condition of the patient got better. We also planned steroid therapy for 6 months by tapering the dosage slowly. After steroid therapy, full recovery of pulmonary functions achieved, and the patient is observed in our outpatient clinic with lack of any pulmonary symptoms.

Mycophenolate mofetil versus azathioprine in the maintenance therapy of lupus nephritis.

BACKGROUND: Renal involvement is one of the major determinants of the outcome in patients with systemic lupus erythematosus. Renal involvement contributes to both morbidity and mortality of the patients as well as indirectly through side effects of therapy directed at the renal lesions. The aim of the study was to evaluate the efficacy of mycophenolate mofetil (MMF) and azathioprine (AZA) in the maintenance therapy of lupus nephritis. METHODS: Thirty-two patients from our center with diagnosed lupus nephritis World Health Organization Class III, IV, V were treated with IVC (0.75-1g/month) for six months in addition to steroid therapy, and then with AZA (n = 15) or MMF (n = 17) as a maintenance therapy. The efficacy of two drugs was compared with changes in serum creatinine, creatinine clearance, 24 hour urine protein excretion, cholesterol, anti-dsDNA antibody, and urine sediment. RESULTS: Mean follow-up time was 41.5 + 7 months. The total remission occurred in 84% of patients (82% with MMF and 87% with AZA), with a complete remission rate of 59.3% (58% with MMF and 60% with AZA) and a partial remission rate of 25% (22% with MMF and 27% with AZA). The urinary protein excretion before MMF treatment was 1.9 + 1 g/dL and decreased significantly to 0.91 + 0.6 g/dL (p = 0.028) after treatment, and decreased from 1.58 + 0.7 g/dL to 0.4 + 0.23 g/dL in the AZA group (p = 0.04). The serum creatinine level decreased from 1.32 + 0.7 mg/dL to 1.12 + 0.68 mg/dL in the MMF group (p = 0.23), and decreased from 0.91 + 0.23 mg/dL to 0.88 + 0.23 mg/dL in the AZA group (p = 0.49). There was no significant change between two groups (p = 0.1). The serum cholesterol decreased from 229 + 57 mg/dL to 171 + 9 mg/dL (p = 0.002), and serum triglyceride level decreased from 228 + 116 mg/dL to 98 + 35 mg/dL (p = 0.004) in the MMF treatment, but no significant change was seen in AZA group. There was no significant difference between the two groups considering the rates of doubling of serum creatinine, progression to end-stage renal failure, relapses, and documented side effects, as well. CONCLUSION: Both therapeutic approaches with MMF or AZA, in combination with corticosteroids, are effective as a maintenance therapy for lupus nephritis.

Mycophenolate mofetil treatment for therapy-resistant glomerulopathies.

BACKGROUND: The management of steroid-resistant glomerulopathies remains a clinical problem. In this trial, we report a clinical observation of 43 patients treated with mycophenolate mofetil (MMF) for steroid-resistant glomerulopathies. METHODS: All patients underwent renal biopsies, and immunofluorescence and light microscopy examinations were conducted in all cases. All patients had been treated with prednisone at a dose of 1 mg/kg per day for at least 8 weeks. Of the 43 patients, 16 were treated with cyclophosphamide and five were treated with cyclosporine A before MMF started. The primary study outcomes were the change in the urinary protein excretion, serum creatinine, comparing the levels at the start of MMF treatment with those at the end of the MMF treatment period. Changes in renal function were also estimated with Modification of Diet in Renal Failure calculation. Wilcoxon signed-ranks test was used as appropriate to compare data from the start with data at the end of the treatment period. RESULTS: The primary glomerular diseases represented included membranoproliferative glomerulonephritis in 23.2%, membranous glomerulonephritis in 18.6%, IgA nephropathy in 13.9%, focal segmental glomerulosclerosis in 9.3%, lupus nephritis (systemic lupus erythematosus) in 25.6% and pauci-immune glomerulopathy in 9.3% of patients. The mean follow-up time was 28.9+/-12 months. Before MMF treatment, 16 patients (37%) had nephrotic range proteinuria and 11 (26%) had renal insufficiency. The urinary protein before MMF treatment was 3.3+/-2.6 g/dL (0.6-9.6) and decreased significantly to 0.87+/-1.1 g/dL (0-5.5) at the end of the MMF treatment period (P=0.02). During treatment, complete remission was seen in 27 patients, partial remission in 10 patients and MMF failure in six patients. The serum creatinine level decreased significantly from 1.29+/-0.55 mg/dL (0.6-3.0) to 1.14+/-0.38 mg/dL (0.5-2.4) post MMF therapy (P=0.046). Using the four-variable Modification of Diet in Renal Failure formula, the glomerular filtration rate increased from 71.5+/-28 mL/min per 1.73 m2 to 78.1+/-27 mL/min per 1.73 m2 (P=0.021). Renal insufficiency resolved in seven of the 11 (63.6%) patients with renal insufficiency initially, two with membranoproliferative glomerulonephritis, two with membranous glomerulonephritis, one with focal segmental glomerulosclerosis, four with pauci-immune glomerulopathy, two with systemic lupus erythematosus nephritis, and in two patients de novo renal insufficiency developed. CONCLUSION: In general, MMF was well tolerated, and most of the patients achieved remission and improvement of renal functions. MMF treatment appeared to offer benefits to problematic patients refractory to conventional therapies for glomerulopathies.

The effect of dialytic modalities on clinical outcomes in ESRD patients with familial Mediterranean fever.

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease seen primarily in Sephardic Jews, Turks, and Armenians. The disease manifests as recurrent attacks of fever and serositis. The most important complication of FMF is the development of renal failure due to AA type amyloidosis. There has not been extensive experience with renal replacement therapy in FMF amyloidosis. Nevertheless, there may be a concern about the possibility of higher rates of morbidity and mortality in amyloidotic patients maintained on chronic hemodialysis. Moreover, there is not enough experience regarding patients on chronic peritoneal dialysis. As a result, the best treatment modality of end-stage renal disease (ESRD) in these circumstances still remains unclear. This study aimed to compare the effect of hemodialysis and peritoneal dialysis modalities on clinical outcomes in ESRD patients associated with FMF amyloidosis. METHODS: Forty FMF patients with ESRD due to amyloidosis were retrospectively analyzed. All 40 patients were on renal replacement therapy, 20 on hemodialysis (HD), 20 on peritoneal dialysis (PD). Peritoneal solute transport rates, weekly mean creatinine clearance, and daily mean ultrafiltration (UF) of the patients on chronic peritoneal dialysis were evaluated. Weekly dialysis durations, dialysis membrane properties, Kt/V values, interdialytic weight gains, and frequency of hypotension during dialysis were evaluated on hemodialysis patients. All of the patients were examined according to their demographic characteristics, laboratory results, duration time on dialysis, erythropoietin requirements, frequencies of infectious complications requiring hospitalization, and the two renal replacement modalities mentioned above were compared in terms of these parameters. RESULTS: Serum albumin levels of the patients with FMF amyloidosis who were maintained on peritoneal dialysis treatment were lower (2.87 vs 3.45) and the frequency of infections of the same group was higher (4.2 vs 0.5) than the patients with ESRD secondary to other diseases in the CAPD group. CONCLUSIONS: This retrospective analysis showed that peritoneal dialysis may have some disadvantages in amyloidotic patients. Due to the high frequency of hypoalbuminemia and infectious complications seen in this group, peritoneal dialysis is widely accepted as an alternative choice of treatment when hemodialysis is not appropriate.

The changes in serum leptin, body fat mass and insulin resistance after renal transplantation.

BACKGROUND: In this prospective-controlled study, we aimed to investigate the effect of changes in insulin resistance and anthropometrical parameters on serum leptin levels (SLL) after renal transplantation (Tx). PATIENTS AND METHODS: Thirty-four patients (M/F: 19/15, mean age: 29 +/- 9 yr) and 30 age and sex-matched healthy controls (C) were included. Body weight, subscapular, suprailiac, periumbilical, biceps and triceps skinfold thicknesses, neck, wrist, hip and waist circumferences, as well as body mass index and body fat mass were measured as anthropometrical parameters. In order to measure the serum glucose, insulin and SLL, blood samples were obtained before and 1 wk, 1 and 6 months after Tx. Homeostasis Model Assessment (HOMA) values were calculated as an index of insulin resistance. RESULTS: Serum leptin levels (SLL) of the patients at pre-Tx were significantly higher than C (21.5 +/- 3.5 vs. 7.8 +/- 0.9 ng/mL, p = 0.002) and decreased at first week after Tx (from 21.5 +/- 3.5 to 8.4 +/- 1.5 ng/mL, p < 0.001). Thereafter, it gradually increased to 12.8 +/- 2.1 ng/mL in the first month and to 14.4 +/- 2.1 ng/mL in the sixth month after Tx. Serum leptin levels at sixth month were significantly higher than C (p = 0.005). Serum insulin and HOMA values changed similar to SLL after Tx. Correlations between SLL and HOMA persisted during the study period [pre-Tx (r: 0.40) and at first (r: 0.38) and sixth (r: 0.47) months]. In linear regression analysis, HOMA and fat mass were found as independent variables for predicting SLL at the sixth month after Tx. CONCLUSION: Serum leptin levels dramatically decreased immediately after Tx and significantly correlated with serum insulin levels and HOMA during the entire study. Increase in SLL at sixth months was probably because of increase in fat mass, insulin resistance and steroid use in renal transplant recipients.