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.

Influence of conversion from calcineurin inhibitors to everolimus on fibrosis, inflammation, tubular damage and vascular function in renal transplant patients.

BACKGROUND: Conversion from calcineurin inhibitor (CNI) to mTOR inhibitors may reduce and even halt the progression of chronic allograft dysfunction (CAD) which is the most important cause of renal allograft loss. We aimed to investigate the effects of conversion from CNI to everolimus on parameters of fibrosis, inflammation, glomerulotubular damage and vascular functions in renal transplant recipients. METHODS: Fifteen stable renal transplant recipients who were under CNI treatment (male/female 13/2, mean age 41 ± 10 years) were enrolled and switched to everolimus. Serum and urinary transforming growth factor-ß (TGF-ß), urinary neutrophil gelatinase-associated lipocalin (NGAL) and monocyte chemoattractant protein-1 (MCP-1) were measured as markers of fibrosis, tubular damage and inflammation. As parameters of vascular functions, pulse wave velocity (PWV), augmentation index (AIx), serum asymmetric dimethyl-arginine and fibroblast growth factor-23 (FGF-23) were measured. All these measurements were repeated at the 3rd month of conversion. RESULTS: Estimated GFR (52 ± 7-57 ± 11 ml/min/l.73 m(2), p = 0.02) (was increased after conversion to everolimus. However, serum uric acid levels were significantly decreased (6.21 ± 1.21-5.50 ± 1.39 mg/dL, p = 0.01). Serum TGF-ß levels (8727 ± 2897-1943 ± 365 pg/mL, p = 0.03) and urinary NGAL levels (26 ± 10-12 ± 2 ng/mg creatinine, p = 0.05) were significantly decreased. However, urinary MCP-1, FGF-23, PWV and AIx did not change. Urinary TGF-ß was associated with urinary NGAL (r = 0.62, p = 0.01), urinary MCP-1 (r = 0.68, p = 0.005) and proteinuria (r = 0.50, p = 0.05). CONCLUSION: Conversion from CNI to everolimus resulted in significant decreases of serum TGF-ß and urinary NGAL which may represent less fibrosis and tubular damage. Association of urinary TGF-ß with NGAL and MCP-1 suggests that tubular damage, fibrosis and inflammation may act together for progression of CAD.

Effects of incremental peritoneal dialysis with low glucose-degradation product neutral pH solution on clinical outcomes.

PURPOSE: Incremental peritoneal dialysis (IPD) could decrease unfavorable glucose exposure results and preserve (RKF). However, there is no standardization of dialysis prescriptions for patients undergoing IPD. We designed a prospective observational multi-center study with a standardized IPD prescription to evaluate the effect of IPD on RKF, metabolic alterations, blood pressure control, and adverse outcomes. METHODS: All patients used low GDP product (GDP) neutral pH solutions in both the incremental continuous ambulatory peritoneal dialysis (ICAPD) group and the retrospective standard PD (sPD) group. IPD patients started treatment with three daily exchanges five days a week. Control-group patients performed four changes per day, seven days a week. RESULTS: A total of 94 patients (47 IPD and 47 sPD) were included in this study. The small-solute clearance and mean blood pressures were similar between both groups during follow-up. The weekly mean glucose exposure was significantly higher in sPD group than IPD during the follow-up (p < 0.001). The patients with sPD required more phosphate-binding medications compared to the IPD group (p = 0.05). The rates of peritonitis, tunnel infection, and hospitalization frequencies were similar between groups. Patients in the sPD group experienced more episodes of hypervolemia compared to the IPD group (p = 0.007). The slope in RKF in the 6th month was significantly higher in the sPD group compared to the IPD group (65% vs. 95%, p = 0.001). CONCLUSION: IPD could be a rational dialysis method and provide non-inferior dialysis adequacy compared to full-dose PD. This regimen may contribute to preserving RKF for a longer period.

Cardiac biomarkers and noninvasive predictors of atherosclerosis in chronic peritoneal dialysis patients.

BACKGROUND: We investigated the relationship among serum cardiac biomarkers including N-terminal pro-brain natriuretic peptide (NT-pro-BNP), cardiac troponin T (cTnT), uric acid and high-sensitive C-reactive protein (hs-CRP) and noninvasive predictors of atherosclerosis including carotid intima-media thickness (IMT), aortic stiffness (pulse wave velocity (PWV)) and transthoracic coronary flow reserve (CFR) in peritoneal dialysis (PD) patients. METHODS: 37 PD patients were included in the study. We measured (1) carotid IMT, (2) PWV and augmentation index (AIx), and (3) CFR. Simultaneous measurements of serum NT-pro-BNP, cTnT, uric acid and hs-CRP were also performed. Associations among these variables were analyzed. RESULTS: cTnT was significantly associated with carotid IMT (r = 0.747, p < 0.001), PWV (r = 0.431, p = 0.035) and CFR (r = -0.439, p = 0.007). In multivariate analysis, cTnT was a significant independent predictor of carotid IMT (ß = 4.446, p < 0.001) and CFR (ß = -2.272, p = 0.013). Patients with high cTnT levels (≥0.01 ng/ml) significantly hadhigher carotid IMT and PWV values. Only the aortic PWV significantly correlated with residual renal function (r = -0.574, p = 0.004). CONCLUSIONS: Serum cTnT appeared to be a useful clinical biomarker for evaluating noninvasive predictors of atherosclerosis in chronic PD patients. Arterial stiffness as determined by PWV is also correlated with residual renal function.

Outcome of Renal Transplantation in Patients With Diabetes Mellitus: A Single-Center Experience.

BACKGROUND: An increasing proportion of kidney recipients have diabetes mellitus (DM). Some concerns have been raised about the kidney transplantation results in diabetic patients. Therefore, we assessed the effect of DM on morbidity and mortality of diabetic patients with renal transplantation. METHODS: We retrospectively studied adult patients with and without DM who underwent living donor transplantation between 2007 and 2016. Information concerning demographic and clinical data were retrospectively analyzed by reviewing the patient files. RESULTS: Of the 1536 transplant recipients, 126 (8%) had diabetes mellitus (mean age 49.4 ± 11.8) and 525 patients were evaluated in the non-diabetic control group (mean age 36.2 ± 15.9). The diabetic and non-diabetic patient groups had a mean follow-up after kidney transplantation 42.5 months (0.27-101.7 months) and 58.8 ± 10.6 months, respectively. In the diabetic patient group, only 3 patients had lost graft and 13 patients were exitus. Three patients had lost graft and 5 patients were exitus in non-diabetic patient group. Cardiac death (54.5%) was the most common cause of mortality in diabetic group. The 6-year patient and graft survival rates are 84.9% and 95.3%; 97.5% and 97.2% in the diabetic and non-diabetic patient groups, respectively. CONCLUSIONS: Both infection and cardiovascular diseases increase morbidity and mortality in renal transplant patients with diabetes mellitus. The mortality risk of diabetic patients after renal transplantation is higher than the non-diabetic kidney recipients. Therefore, diabetic patients need meticulous cardiac evaluation before renal transplantation and a close follow-up, in terms of infection, after transplantation.

COVID-19 Infection in Kidney Transplant Recipients: A Single Center Experience.

BACKGROUND: Kidney transplant recipients appear to be particularly high risk for critical COVID-19 illness owing to chronic immunosuppression and coexisting conditions. The aim of this study is to present the clinical characteristics and outcomes of our hospital's kidney transplant recipients who were hospitalized due to COVID-19 infection. METHODS: In our retrospective observational study of COVID-19 PCR-positive patients, 31 of them were hospitalized with COVID-19 pneumonia and they were evaluated using demographics, laboratory data, treatment, and outcome. The prognostic nutritional index (PNI), which is calculated using the serum albumin concentration and total lymphocytic count, was also evaluated. The baseline immunosuppressive therapy of patients at the time of admission and the treatments they received during their hospitalization were recorded. All patients were treated with favipiravir. RESULTS: Of the 31 renal transplant patients with COVID-19 pneumonia, 20 were male and the mean age was 52.7 ± 13.4. Nine (29%) of the patients died. All patients were treated with favipiravir for 5 days; laboratory tests were recorded before and after treatment. The mean PNI of the patients who survived was higher than the patients who died. CONCLUSIONS: The 9 patients who died had lower PNI and higher neutrophil-to-lymphocyte ratio (NLR), creatinine, l-lactate dehydrogenase (LDH), ferritin, and C-reactive protein (CRP) levels. Hospitalized kidney transplant recipients with COVID-19 have higher rates of mortality. The PNI exhibited good predictive performance and may be a useful clinical marker that can be used for estimating survival in COVID-19 patients.

Elevated resistin levels are associated with inflammation in hemodialysis patients with failed renal allografts.

BACKGROUND: Resistin is an adipocytokine, associated with insulin resistance and inflammation. The aim of this study is to evaluate the levels of serum resistin levels and other markers of inflammation in hemodialysis (HD) patients with failed renal allografts. METHODS: Sixty-nine HD patients with failed renal allografts and 98 never transplanted (naive) HD patients and also 21 healthy controls were included in the study. Serum levels of various biochemical parameters as well as resistin, IL-6, TNF-α and hs-CRP as biochemical markers of inflammation, were measured. RESULTS: Serum resistin levels in patients with failed renal allografts (4.80 ± 2.06 ng/mL) were significantly higher than those of the naive HD patients (3.44 ± 1.48 ng/mL) and healthy controls (0.95 ± 0.38 ng/mL; p<0.001). Patients with failed transplants were also characterized by higher TNF-alpha levels (96.8 ± 131.3 pg/mL vs. 40.9 ± 25.4 pg/mL; p<0.001) and IL-6 levels (83.9 ± 150.9 pg/mL vs. 14.6 ± 14.4 pg/mL; p<0.001) as compared to naive HD patients. Serum hs-CRP levels in patients with failed renal allografts (9.33 ± 11.86 mg/L) were significantly higher than those of the naive HD patients (1.26 ± 1.71 mg/L) and healthy controls (2.12 ± 1.82 mg/L; p<0.001). Serum albumin levels in patients with failed transplants (3.84 ± 0.47 g/dL) were lower as compared to never transplanted HD patients (4.13 ± 0.33 g/dL) and healthy controls (4.53 ± 0.40 g/dL; p<0.001). There was a positive correlation between serum resistin and TNF-alpha levels (r = 0.486, p<0.001). CONCLUSIONS: Serum resistin levels are increased in HD patients with failed renal allografts very probably reflecting an allograft-induced chronic inflammatory state.

Pauci-immune necrotizing crescentic glomerulonephritis with crescentic and full moon extracapillary proliferation: clinico-pathologic correlation and follow-up study.

The prognostic value of the type and extent of extracapillary proliferation (ECP) in pauci-immune necrotizing crescentic glomerulonephitis (PIGN) was evaluated in this study. In 141 PIGN cases, all glomeruli with ECP were grouped according to type (cellular, fibrocellular and fibrous) and extent of the lesions in Bowman's space; (segmental, semicircumferential and circumferential, which might be termed full moon-FM). Cases with cellular and fibrous lesions involving ≥ 50% of glomeruli with ECP were classified as cellular and fibrous groups, respectively, while the remaining cases were classified as fibrocellular. Cases with segmental and circumferential (FM glomerulus) lesions involving ≥ 50% of glomeruli with ECP were classified as ECPI and ECPIII (FM) groups, respectively, while the rest were classified as ECPII. All the cases were classified according to Berden et al. Significant results were only nearly obtained for the FM group, including the need for dialysis. The Cox regression model revealed a 2.6-fold risk for FM cases regarding dialysis requirement. We propose that the percentage of FM glomeruli should be noted in the pathology report, and cases with more than 50% of FM glomeruli (FM group) should be identified in the group with increased risk of dialysis requirement. Our series also suggests that classification according to Berden et al. is of clinical relevance.

Colonic necrosis and perforation due to calcium polystyrene sulfonate in a uraemic patient: a case report.

Sodium or calcium polystyrene sulfonate (Kayexalate or analog) is an ion-exchange resin commonly used to treat hyperkalaemia in patients with chronic kidney disease. It is known to cause digestive complications, such as nausea, vomiting and constipation. Although rare, colonic necrosis and perforation are very severe complications associated with the medication. In this case report, we present a case of calcium polystyrene sulfonate-induced colonic necrosis and perforation to remind clinicians of this rare, but dangerous, toxicity associated with this commonly used medication.

Effect of LMO2 protein expression on survival in chronic myeloid leukemia patients treated with imatinib mesylate.

LIM domain only-2 (LMO2) is an important regulator of hematopoietic stem cell development. LMO2 protein is expressed in all three hematopoietic lineages precursors of the hematopoietic system, and its expression has been shown to decrease gradually during differentiation. Chronic myeloid leukemia (CML) is a malignant clonal myeloproliferative disorder in which the terminal differentiation is not altered until the appearance of an accelerated or blast phase. We examined whether LMO2 protein expression can predict outcome CML patients undergoing tyrosine kinase inhibitor therapy, imatinib mesylate (IM). Immunohistochemistry on bone marrow biopsy material for LMO2 protein was performed in 47 CML patients. We report that the LMO2 protein expression is correlated with improved hematologic remission and overall survival in the CML patients treated with IM. The immunohistologic analysis of LMO2 protein expression may become a predictive factor for anticipating the treatment responses of CML patients.

Effect of pathologic fractures on survival in multiple myeloma patients: a case control study.

BACKGROUND: Multiple Myeloma (MM) is a B cell neoplasm characterized by the clonal proliferation of plasma cells. Skeletal complications are found in up to 80% of myeloma patients at presentation and are major cause of morbidity. METHODS: 49 patients were enrolled with MM admitted to Black Sea Technical University Hospital between 2002-2005. Pathologic fractures (PFs) were determined and the patients with or without PF were followed up minimum 3 years for survival analysis. RESULTS: PF was observed in 24 patients (49%) and not observed in 25 patients (51%). The risk of death was increased in the patients with PF compared with patients who had no fractures. While overall survival was 17.6 months in the patients with PFs, it was 57.3 months in the patients with no PFs. CONCLUSION: These findings suggest that PFs may induce reduced survival and increased mortality in the MM patients, however, larger sample size is essential to draw clearer conclusions added to these data.