Clinical Presentation and Determinants of Mortality of Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: A Multinational Cohort Study.

The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study 112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six- and 12-week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio [HR]: 2.29; p-value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p-value = 0.017) were independent predictors for 6-week all-cause mortality, whereas the initial use of a voriconazole-based regimen showed a protective effect (HR: 0.34; p-value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.

Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case-Control Study.

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.

A form of apolipoprotein a-I is found specifically in relapses of focal segmental glomerulosclerosis following transplantation.

Recurrence of idiopathic focal segmental glomerulosclerosis (FSGS) following kidney transplantation occurs in a large percentage of patients. Accurate prediction of recurrence and elucidation of its pathogenesis are major therapeutic goals. To detect differential proteins related to FSGS recurrence, proteomic analysis was performed on plasma and urine samples from 35 transplanted idiopathic FSGS patients, divided into relapsing and nonrelapsing. Several proteins were detected increased in urine of relapsing FSGS patients, including a high molecular weight form of apolipoprotein A-I, named ApoA-Ib, found exclusively in relapsing patients. This finding was verified by Western blot individually in the 35 patients and validated in an independent group of 40 patients with relapsing or nonrelapsing FSGS, plus two additional groups: FSGS-unrelated patients showing different proteinuria levels (n = 30), and familial FSGS transplanted patients (n = 14). In the total of 119 patients studied, the ApoA-Ib form was detected in 13 of the 14 relapsing FSGS patients, and in one of the 61 nonrelapsing patients. Only one of the 30 patients with FSGS-unrelated proteinuria tested positive for ApoA-Ib, and was not detected in familial patients. Urinary ApoA-Ib is associated with relapses in idiopathic FSGS and warrants additional investigation to determine its usefulness as biomarker of relapse following transplantation.

Efficacy and safety of conversion from twice-daily to once-daily tacrolimus in a large cohort of stable kidney transplant recipients.

Prolonged-release tacrolimus was developed to provide a more convenient once-daily dosing that could improve patient adherence. We conducted a multicenter, prospective, observational, 12-month study to describe the efficacy, safety and patient preference of conversion from tacrolimus twice-daily to once-daily formulation in stable kidney transplant recipients in routine clinical practice. Conversion was made on a 1 mg: 1 mg basis (1 mg: 1.1 mg in patients with trough levels <6 ng/mL). The study included 1832 patients (mean age (± SD): 50.0 ± 13.4 years; 62.7% male). After conversion, a modest reduction in tacrolimus trough levels, necessitating an increase in daily dose, was observed (mean changes at 12 months of -9.1% and +1.24%, respectively; p < 0.0001). Mean glomerular filtration rate did not change significantly (56.5 ± 19.7 mL/min at conversion vs. 55.7 ± 20.6 mL/min at 12 months). Proteinuria, blood pressure, lipid, hepatic and glucose parameters remained stable. Eight patients (0.4%) had acute rejection and 34 patients (1.85%) discontinued treatment. Almost all patients (99.4%) preferred the once-daily formulation, because of less frequent dosing (66%) and improved adherence (34%). In conclusion, at similar doses to twice-daily tacrolimus, once-daily formulation provided stable renal function, a low acute rejection rate, and good tolerability in stable kidney transplant recipients in the routine clinical practice setting.

[Post-transplant diabetes mellitus depending on the pre-transplant dialysis technique]. / Diabetes mellitus post-trasplante según técnica de diálisis previa al trasplante.

Post-transplant diabetes mellitus (PTDM) is one of the most important complications in kidney transplant patients because it has a significant impact on graft and patient survival. Diagnosis of PTDM should be based on the American Diabetic Association criteria. Recent studies show the value of performing an oral glucose tolerance test in all patients. Multiple risk factors promote PTDM. PTDM incidence may be reduced by controlling modifiable factors (immunosuppression, obesity, infections...). According to RMRC data, patients on peritoneal dialysis are younger, but have a greater incidence rate of dyslipidemia and obesity. Recent data suggest that subclinical information, adiponectin, and ghrelin may be a significant pathogenetic factor in development of insulin resistance and diabetes mellitus. There is no clear evidence that the dialysis procedure influences the subclinical inflammatory state and adipocytokines. According to data from the Spanish group for the study of PTDM, a relationship exists between ghrelin levels and sex in patients on peritoneal dialysis. The most common metabolic complication in patients on peritoneal dialysis is hyperglycemia. Pre-transplant hyperglycemia promotes the occurrence of PTDM. There is no clear evidence in the literature showing that the dialysis procedure is a risk factor for the occurrence of PTDM. Additional multicenter studies are required to analyze the clinical and biological characteristics of renal patients and their relationship to PTDM.

Multinational case-control study of risk factors for the development of late invasive pulmonary aspergillosis following kidney transplantation.

OBJECTIVES: To assess the risk factors for development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT). METHODS: We performed a multinational case-control study that retrospectively recruited 112 KT recipients diagnosed with IPA between 2000 and 2013. Controls were matched (1:1 ratio) by centre and date of transplantation. Immunosuppression-related events (IREs) included the occurrence of non-ventilator-associated pneumonia, tuberculosis, cytomegalovirus disease, and/or de novo malignancy. RESULTS: We identified 61 cases of late (>180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p <0.001) within the 6 months prior to the onset of late IPA. After multivariate adjustment, previous occurrence of IRE (OR 19.26; 95% CI 2.07-179.46; p 0.009) was identified as an independent risk factor for late IPA. CONCLUSION: More than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. We identified some risk factors that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA.

Subclinical inflammation in renal transplant recipients: impact of cyclosporine microemulsion versus tacrolimus.

BACKGROUND: Renal insufficiency and renal transplant (RT) provoke a microinflammatory state that leads to increased atherosclerosis. It is not fully known whether calcineurin inhibitors (CNIs) play a role in the inflammation observed in these patients or whether any differences exist between CNIs. OBJECTIVES: The study aimed to establish differences in the inflammatory state of two groups treated with cyclosporine microemulsion (CyA) or tacrolimus (TC). PATIENTS AND METHODS: This prospective study included 81 RT patients divided into two groups according to the CNI: CyA group, n = 35 versus TC group, n = 46. The markers of inflammation (MIF) were determined preRT and at 3 and 12 months' postRT: C-reactive protein (CRP), serum amyloid protein A (SAA), interleukin-6 (IL-6), soluble interleukin-2 receptor (sIL-2R), tumor necrosis factor-alpha (TNF-alpha), and pregnancy-associated plasma protein A (PAPP-A). Samples were collected in stable patients in the absence of rejection, active infection, or inflammatory processes. RESULTS: No significant differences existed between the markers of inflammation in the two treatment groups prior to transplantation. At 3 months' posttransplant, patients treated with CyA showed significantly higher levels of IL-6 (P = .05), SAA (P = .03), and sIL-2R (P = .008) compared with patients treated with TC. These differences were maintained for IL-6 (P = .03) and sIL-2R (P = .027) at 12 months' posttransplant. A multivariate analysis at 3 months showed that only age [OR 10.1; CI (95% 2.6-38.4); P = .001], SAA [OR 4.8; IC (95% 1.4-16.5); P = .015], and sIL-2R [OR 4.9; IC (95% 1.5-16.2); P = .009] were independent predictors of the CNI used. At 12 months, age [OR 3.7; IC (95% 0.9-14.2] and sIL-2R [OR 6.04; IC (95% 1.5-23); P = .006] continued to be independent predictors. CONCLUSIONS: Patients treated with CyA displayed significantly higher levels of inflammatory markers (IL-6, SAA, sIL-2R) at 3 and 12 months' posttransplantation, independent of age, gender, time on dialysis, diabetes mellitus (preRT and de novo postRT), and renal function measured by serum creatinine.

Do anti-CD25 monoclonal antibodies potentiate posttransplant diabetes mellitus?

UNLABELLED: Anti-CD25 monoclonal antibodies (MAbs) are directed against the IL-2 (CD-25) receptor, which is associated with the pathogenesis of diabetes mellitus (DM). Measuring CD25 on peripheral blood lymphocytes could be a new immunologic marker to identify patients with prediabetes. OBJECTIVE: The study aimed to analyze whether administration of anti-CD25 MAbs was an independent risk factor for posttransplant diabetes mellitus (PTDM) in kidney transplant (KT) patients at 3 months after transplantation. PATIENTS AND METHODS: Seventy-four stable, nondiabetic KT patients were included in the study. The overall sex distribution was 70% men and mean overall age, 52 +/- 10 years. Thirty-eight subjects where treated with anti-CD25 antibodies (basiliximab). The diagnosis of PTDM was made if patients required insulin or oral antidiabetic drugs and/or had glycemia >200 mg/dL at 120 minutes after an oral glucose tolerance test (75 g glucose). We determined the age, weight, body mass index, acute rejection, chronic hepatitis C virus (HCV) infection, and type of calcineurin inhibitor. RESULTS: Thirty-four percent of patients developed PTDM. Patients treated with anti-CD25 antibodies were older (P = .022) and showed a greater incidence of PTDM (P = .041). The logistic regression analysis (dependent variable: PTDM; independent variables: age, anti-CD25, tacrolimus vs cyclosporine) showed that treatment with anti-CD25 is an independent risk factor for PTDM (P = .041; OR 3.28; CI 95% 1.04-10.31). CONCLUSION: Patients treated with anti-CD25 MAbs showed greater incidence of PTDM.

Atorvastatin treatment in the short term: does it induce renoprotection or vasculoprotection in renal transplantation?

INTRODUCTION: Proteinuria and dyslipidemia are nonimmune risk factors implicated in the deterioration of kidney function and associated with an increased risk of accelerated atherogenesis. Statin therapy, used for cholesterol reduction, has shown a renoprotective effect in animal models, particularly in cases of proteinuria. This may occur through lipid-independent mechanisms, such as improved endothelial dysfunction/vascular biology, reduced inflammatory cytokine production (transforming growth factor-beta 1 [TGF-beta1]), and regulation of fibrogenic responses. We studied mechanisms of action of agents, such as statins, to change proteinuria, inflammatory parameters, and TGF-beta1 plasma levels in relation to vascular tone. METHODS: Fifty-six kidney transplant recipients (30 men and 26 women of overall mean age 54 +/- 13 years) were treated posttransplantation with atorvastatin (10 mg/d) for 12 weeks without renin-angiotensin-system blockade drugs. Inflammatory variables, biochemical parameters, lipid profile, renal function, and TGF-beta1 levels were determined at baseline and at 3 months. Vascular stiffness was evaluated using pulse wave velocity (PWV). RESULTS: Baseline TGF-beta1 plasma levels were higher among transplant recipients than healthy controls, namely 8.12 ng/mL (range, 5.82-13.12) to 2.55 (range, 1.78- 4.35) (P < .01). Furthermore, the levels remained higher after the treatment with atorvastatin, namely, 7.59 (range, 4.97-12.35) to 2.55 (range, 1.78-4.35) ng/mL (P < .01). Atorvastatin treatment significantly decreased total cholesterol as well as low-density lipoprotein cholesterol plasma levels, but did not modify mean blood pressure (MBP), proteinuria, creatinine clearance, or inflammatory factors. Reduction in TGF-beta1 plasma levels was statistically significant among patients with PWV >9.75 (m/s) (pathology reference value) namely, from 10.7 ng/mL (range, 7.02-13.98) to 6.7 (range, 3.96-11.94) (P = .038). Among older patients, atorvastatin significantly decrease TGF-beta1 plasma levels: from 9.5 ng/mL (range, 6.45-14.44) to 5.65 (range, 3.63-9.48; P < .05). The decreased TGF-beta1 was not related to changes in lipid profiles. CONCLUSIONS: Atorvastatin (10 mg/d) improved the lipid profile and moreover among older patients with worse PWV (>9.75 m/s), TGF-beta1 levels were significantly reduced. Our results suggested that statins displayed potent actions distinct from their hypolipidemic effects.

Prognostic Value of Modified Banff Score in the Evolution of Renal Function.

BACKGROUND: Some lesions not included in the Banff classification, such as inflammation in the scarred areas and total inflammation, have been described to have prognostic value in the evaluation of graft biopsies. Our aim was to reassess kidney graft biopsies and study the impact of histopathologic lesions, both those graded in the Banff classification and those related to inflammation, on the graft function and evolution. METHODS: We selected 20 biopsies exhibiting chronic pathology without a specific phenotype, and we reevaluated them with the use of a modified Banff score. RESULTS: We found statistically significant association between the presence of total inflammation (P = .048; P = .038), the presence of inflammation in scared area (P = .037; P = .018), and creatinine at the time of renal biopsy and 1 year after the renal biopsy, respectively. CONCLUSIONS: Our results suggest that the presence of both inflammation in the scarred areas and total inflammation are related to renal function at the time of the biopsy and to renal function 1 year after the biopsy.

Effect of low doses of atorvastatin on adiponectin, glucose homeostasis, and clinical inflammatory markers in kidney transplant recipients.

INTRODUCTION: Various studies describe the pleiotropic antiinflammatory and antioxidant effects of atorvastatin, in addition to its hypolipemic effects. It has been suggested that statins modify glucose homeostasis via their antiinflammatory effects. A further hypothesis suggests that the incidence of posttransplantation diabetes is lower in statin-treated patients. This study sought to ascertain whether atorvastatin modifies glucose homeostasis, adiponectin, and inflammatory markers in kidney transplant recipients. PATIENTS AND METHODS: Sixty-eight kidney transplant recipients (41 men, 27 women; mean age, 53 +/- 12 years) with stable renal function and dyslipidemia were treated with atorvastatin (10 mg/d) for 12 weeks. Glucose, insulin, homeostasis model assessment (HOMA-IR) index, adiponectin, tumor necrosis factor (TNF)-alpha, and serum C-reactive protein (CRP) concentrations were determined at baseline and at 3 months. The lipid profile, renal function parameters (creatinine, creatinine clearance, and proteinuria), as well as GOT, GPT, and CK were determined at baseline and at 3 months. RESULTS: Treatment with atorvastatin achieved a statistically significant decrease in lipid profile. After 3 months of treatment, 74.6% of patients had total cholesterol and 78.7% low-density lipoprotein (LDL) cholesterol concentrations within reference range (<5.2 and 3.3 mmol/L, respectively). Furthermore, 47.5% of patients attained an LDL concentration <2.59 mmol/L. A greater reduction in total cholesterol (P = .05) and LDL cholesterol (P = .04) was achieved in patients with creatinine clearance <60 mL/min. Atorvastatin did not modify glucose homeostasis parameters, adiponectin, TNF-alpha, or CRP. At baseline and after 3 months of treatment, an inverse correlation was found between adiponectin and glucose, insulin, HOMA- IR index, and creatinine clearance, and a positive correlation was found between adiponectin and high-density lipoprotein (HDL) cholesterol. CONCLUSION: Atorvastatin at a dose of 10 mg/d in kidney transplant recipients does not modify glucose homeostasis or alter inflammatory markers, despite its hypolipemic effects. Its efficacy to reduce total cholesterol and LDL cholesterol was greater in patients with worse renal function.

F2-isoprostanes in kidney transplant patients: relationship with inflammatory markers.

This prospective study evaluated the relationship between inflammation and oxidative stress in a group of dialysis patients just before and 3 months after kidney transplantation and compared the results with a control group of healthy subjects. The oxidative stress markers determined were different F2-isoprostane isomers. The inflammatory markers included C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and pregnancy-associated plasma protein A. Forty-three patients were the study group and 50 healthy subjects from a hospital blood bank as controls. The results showed levels of inflammatory and oxidative stress markers to be higher in the dialysis patients than in the control group, although they improved following kidney transplantation. Finally, significant correlations were observed between F2-isoprostane isomers and inflammatory markers.

[Variability in Epstein-Barr virus serological markers in adult kidney transplant recipients]. / Variabilidad en los marcadores serológicos del virus de Epstein-Barr en receptores adultos de trasplante renal.

Epstein-Barr virus (EBV) infection is associated with the development of post-transplant lymphoproliferative disorders (PTLD). However, the clinical relevance and criteria for EBV serological reactivation in EBV-seropositive transplant recipients is unclear. EBV-specific antibodies: viral capsid immunoglobulm G [IgG (VCA)], nuclear antigen (EBNA) IgG, immunoglobulin M [IgM (VCA)] and early antigen IgG (EA) were prospectively analyzed in 71 adult kidney transplant recipients, before starting immunosuppression, when they were uraemic, and after transplantation. A total of 351 serum samples were tested. Relevance of different EBV reactivation-related variables were analyzed using the chi-square test. In 37 of 71 (52.1%) patients IgM (VCA) or IgG (EA) were detected when they were uraemic. EBV reactivation occurred in 25 of 71 (35.2%) patients, with clinical symptoms (fever, leukopenia, kidney function impairment, and increase in transaminases) in nine cases. One of 71 patients developed a PTLD, without detection of serologically EBV reactivation, but with an increase in EBV viral load. Absence of mycophenolate mofetil, that inhibits lymphocyte proliferation and antibody production, in immunosuppression was statistically significantly associated with EBV reactivation (p = 0.015). Serological diagnosis of EBV reactivation should be based on strict criteria (IgM (VCA) seroconversion, four-fold increase in IgM (VCA) or IgG (EA), or four-fold decrease in IgG (EBNA) titers and on analysis of serial samples. Some EBV-seropositive patients at high risk of developing PTLD could benefit from this diagnostic methodology.

[Histoplasmosis in a renal transplant patient]. / Histoplasmosis en un trasplantado renal.

The case of a Spanish kidney transplant patient who developed disseminated histoplasmosis approximately one year and a half after transplantation without having previously visited or travelled to endemic areas of histoplasmosis is presented. To our knowledge this is the first case of this disease in a kidney transplant patient in Spain without epidemiologic antecedent. The study of anti-histoplasm antibodies by complement fixation of the donor and recipient did not safely clarify the mechanism of contagion.

Outcomes of Monoclonal Gammopathy of Undetermined Significance in Patients Who Underwent Kidney Transplantation.

BACKGROUND: There are few reports about the clinical course and prognosis of monoclonal gammopathy of undetermined significance (MGUS) in long-term immunosuppressed patients. Our aim was to study the association and evolution of MGUS and renal transplantation. METHODS: Subjects submitted to renal transplantation between 1996 and 2011 who presented MGUS before or after immunosuppressive treatment was established were selected. RESULTS: Patients (N = 587) underwent kidney transplantation in our center during the selected period. MGUS was detected in 17 (2.9%) patients (10 men and 7 women with a mean age of 69.9 ± 10.07 years), with a median follow-up of 6 years. All patients had a functioning graft. Nine had MGUS before transplantation. One patient had multiple myeloma, and 8 remained stable. Eight patients had development of MGUS after transplantation. Six patients remained stable, 1 showed no MGUS, and 1 displayed an increased monoclonal component in further controls. CONCLUSIONS: In our study, renal transplantation is not a risk factor for the development of malignant processes in patients with MGUS before transplantation. There is a group of patients who tend to have MGUS after transplantation; nevertheless, they had a benign evolution during a 6-year follow-up.

Recurrent Glomerulonephritis in Renal Transplantation: Experience in Our Renal Transplantation Center.

BACKGROUND: Post-transplant recurrent glomerulonephritis (RGN) is the third cause of graft failure in the first year after renal transplantation (RT). The purpose of this study was to analyze the incidence of RGN, clinical presentation, and clinical evolution of transplanted renal graft in patients who underwent RT at our center. METHODS: We studied patients with glomerulonephritis (GN) who underwent RT (2007 to 2013).We analyzed sex, age, time in dialysis, type of GN, type of RT, time to post-transplant RGN, kidney function at the time of diagnosis of RGN, and renal graft evolution. Renal biopsy samples were processed in the anatomic pathology laboratory. RESULTS: Three hundred sixteen patients received kidney transplantation during this time period. In 83 cases, the reason for transplantation was primary GN. Of these 83 patients, 15 (18%) had RGN confirmed by renal biopsy. Data for these 15 patients include sex: 73.3% men, 26.7% women; mean age: 42.2 (29-73) years; type of RT: 80% cadaveric donor (CD) versus 20% living donor (LD); type of GN: 18.4% immunoglobulin (Ig)A nephropathy, 35.7% membranous GN, 10.53% type I membrano-proliferative GN (MPGN I), and 16.6% focal segmental glomerular sclerosis (FSGS). The mean time to post-transplant RGN was 2 years (1 month to 16 years). Patients who received an LD transplant had a shorter time to post-transplant RGN than those who had a CD transplant. One patient with FSGS and one with MPGN I had a time to post-transplant RGN of less than 1 year. In the evolution of renal function, 33.3% of patients had graft failure. CONCLUSIONS: The incidence of RGN was lower (18%) than that published in the literature. Membranous nephropathy was the most frequent cause of post-transplant RGN. Patients who underwent LD transplantation and those with IgA nephropathy had a shorter interval of time to post-transplant RGN than patients with FSGS and MPGN I.

Late Onset of Cholesterol Embolism Leading to Graft Failure After Renal Transplantation: Report of Two Cases.

Cholesterol-crystal embolization (CE) usually presents as an acute or subacute multisystemic disease. When affecting native kidneys prognosis is poor, often leading to chronic kidney disease. Presentation in renal allografts is a rare condition although probably underdiagnosed. If renal CE originates from the recipient, allograft survival is usually good, whereas if the donor is the origin, graft dysfunction and subsequent graft loss are common. Associated risk factors are common to native and transplanted kidneys. We report 2 renal graft recipients of different cadaveric donors, both male and 68 years old, diagnosed with CE in renal grafts at 19 and 72 months after transplantation, respectively. They presented previous risk factors for CE, including severe atherosclerosis. They presented insidious and asymptomatic impairment of renal function initially. Renal graft biopsy specimens showed CE in the interlobular arteries. Potential triggers for CE were suspended and high doses of steroids were started. However, progressive decline in renal function and requirement of chronic dialysis occurred within the first year after diagnosis in both cases. Herein we discuss the causal or incidental role of CE in the graft failure of these cases, highlighting the serious outcome despite the recipient origin of the CE and the initiation of treatment.

Nodular Arteriolar Hyalinosis as Histopathologic Hallmark of Calcineurin Inhibitor Nephrotoxicity: Does It Always Have the Same Meaning?

INTRODUCTION: Nodular arteriolar hyalinosis (NAH) is a typical, although not specific, histological finding of calcineurin inhibitor toxicity (CNIT). The objective of our study was to assess the reason why some patients showing strong NAH in renal graft biopsies who underwent calcineurin inhibitor (CNI) withdrawal presented very poor outcome whereas others improved graft function. MATERIAL AND METHODS: We performed 207 renal graft biopsies between January 2011 and May 2014 due to clinical criteria. In 13 patients CNI withdrawal was performed, and the major histopathological finding was severe NAH. The results after this action were analyzed. RESULTS: We selected 2 groups: good outcome and poor outcome. Eight patients showed good results including stabilization or improvement of graft function. Five patients presented poor results requiring chronic hemodialysis. C4d staining was negative in all biopsy specimens, and peritubular capillaritis was not observed. To identify potential prognostic markers we retrospectively reviewed biopsy samples looking for minor or nonspecific features, especially inflammation scores both global and on fibrotic areas as per Banff classification. Mean serum creatinine level at time of biopsy and mean arteriolar hyalinosis score did not show significant differences between both groups. In contrast, the poor results group presented a higher mean global inflammation score compared with the good results patients. CONCLUSIONS: NAH is not a risk factor for poor renal graft outcome by itself. Other histopathologic findings, usually considered as secondary markers, like the inflammation score, should be considered before deciding CNI withdrawal.

Are equally spaced specimen collections necessary to assess biological variation? Evidence from renal transplant recipients.

The established method for determining the components of biological variation (BV) requires equispaced time intervals between samplings. In a previous study, we determined BV in renal post transplantation patients, taking advantage of the samples obtained within their clinical treatment protocol (not necessarily equispaced). To confirm the validity of this practice, we sought to determine if the use of varying sampling intervals has an effect on the results obtained in such biological variation studies. The study included two phases: comparison of the results found with identical and non-identical sampling intervals and correlation between the within-subject BV and the length of the sampling interval. There were no differences in within-subject BV between the groups or correlations with sampling intervals for any of the constituents studied. We conclude that samples acquired within established clinical protocols for kidney transplant recipients can be used for estimating BV.

Rhabdomyolysis, oedema and arterial hypertension: different syndromes related to topical use of 9-alpha-fluoroprednisolone.

Over a one year period we detected five cases of iatrogenic mineralocorticoidism secondary to topical application of creams containing 9-alpha-fluoro-prednisolone. Although the same product was involved in all cases, the clinical features differed and included two cases of myopathy and hypokalemic rhabdomyolysis, one of oedema and two of arterial hypertension. Discontinuation of treatment and administration of potassium supplements produced a rapid recovery and all patients remain well six months later.