Serkan Yildiz

Renal medullary changes in renal allograft recipients with raised serum creatinine

Objective: To test the hypothesis that the renal medulla may reflect rejection related changes and thus have a predictive value in the assessment of acute renal allograft rejection or chronic graft damage. Methods: 75 post-transplant biopsies from 57 patients were scored according to the Banff 1997 scheme. The biopsies with adequate cortical and medullary tissue (n = 23) were selected and medullary tissues were reviewed for rejection related lesions except intimal arteritis. Chronic damage was determined by image analysis depending on periodic acid-methenamine silver (PAMS)-Masson trichrome (MT) staining. Medullary and cortical changes were compared. Results: Interstitial inflammation and tubulitis were more frequent and severe in the cortex (p<0.001). Medullary tubulitis was associated with intimal arteritis (p = 0.003, r = 0.598). Medullary interstitial inflammation (n = 8) and tubulitis (n = 4) were associated with cortical borderline changes (n = 5) or allograft rejection (n = 3). The sensitivity, specificity, and positive and negative predictive values of medullary inflammatory changes in predicting cortical allograft rejection were 43%, 69%, 37%, and 73%, respectively. A significant association was observed between medullary MT-SAP and cortical PAMS-SAP values (p = 0.02, R2 = 0.23). Conclusions: Acute rejection related lesions are more common and severe in the cortex, and the renal medulla does not sufficiently reflect cortical rejection. The positive and negative predictive values of medullary changes for allograft rejection are low, and medullary inflammation is not a reliable indicator of allograft rejection. Increased medullary fibrosis is correlated with chronic cortical damage.

IgA nephropathy: association of C4d with clinical and histopathological findings and possible role of IgM.

Abstract Background: In patients with IgA nephropathy (IgAN) lectin and alternative pathways of the complement can be activated. Our aim was to analyze the association of glomerular and extraglomerular C4d staining—the representative of lectin pathway—with demographic, clinical and histopathological findings in primary IgAN patients. Design: Seventy-three patients were enrolled and after re-evaluation 37 of them were included in this study. Biopsies were analyzed for staining with anti-C4d primary monoclonal antibody by immunohistochemistry. Patients were classified as positive and negative groups based on their glomerular C4d deposition. Groups were compared for their baseline clinical and histopathological findings. Results: Sixteen (43.2%) of 37 patients were C4d-positive. Glomerular C4d-staining was associated with more severe proteinuria (2906 mg/day vs. 1091 mg/day; p = 0.002), lower GFR (54.87 mL/min vs. 95 mL/min; p = 0.023), higher blood pressure (p = 0.022), more severe endocapillary hypercellularity (p < 0.001) and more severe tubular atrophy (p < 0.01). Mesangial IgM deposition was found to be associated with glomerular C4d staining and nephrotic range proteinuria. Conclusions: Glomerular C4d deposition was found to be associated with more unfavorable histopathological and clinical findings at the time of diagnosis. Association of mesangial IgM deposition with the activation of lectin pathway is a novel finding. Mesangial IgM deposition in our patients may reflect the genetic heterology of IgAN between diverse populations. However, since these data are about association, a cause-and-effect about IgM and IgAN cannot be proven solely with these findings.

Long-term Follow-up of a Reused Kidney Allograft

To the Editor: More than 28 years have passed since Al-Hasani et al first reported on the reuse of a kidney allograft. However, there are still few long-term follow-up data regarding such reuse. In July 2007, we reported in AJKD a case of successful kidney allograft reuse from a deceased kidney transplant recipient. The first recipient of the transplanted kidney survived 6 years with good kidney function, but in April 2003 experienced an intracranial hemorrhage and was pronounced brain dead in our hospital. A 24-year-old man who had been treated with maintenance hemodialysis for 3 years became the second recipient of the allograft. At the time of writing, 12 years after transplantation, the second recipient has a serumcreatinine level of 1.3 mg/dL (corresponding to an estimated glomerularfiltration rate of 61 mL/min/1.73 m as calculated by theMDRD[ModificationofDiet inRenalDisease] Study equation). Protein andblood are not detectable by standardurinalysis, and24-hour urineprotein excretion is 100 mg/d.Thepatient’s bloodpressure is 130/ 80 mm Hg with treatment with valsartan and carvedilol. His current immunosuppressive regimen includes prednisolone (5 mg/d), azathioprine (50 mg/d), and tacrolimus (1.5 mg/d). We believe that our experience—reuse of a kidney allograft 6 years after the initial transplantation and with excellent allograft function 12 years postretransplantation—shows that previously used allografts are a potential source of kidneys for transplantation when donor-recipient pairs are carefully selected and the immunosuppression protocol is tailored to the original allograft.

A rare case of acute renal infarction due to atrial fibrillation mimicking renal colic

A 70-year-old patient with acute renal infarction due to chronic atrial fibrillation is presented. The clinical presentation of the patient was suggestive of renal colic. Computerized tomography was consistent with acute renal infarction and confirmed the diagnosis. After giving anticoagulation and antiarrhythmic treatment, she was discharged with clinical improvement. High clinical suspicion is necessary on an old patient who has thromboembolic risk factors with the complaint of abrupt-onset flank pain.

Evaluate to the Efficacy and Effectiveness of Different Assessment Methods on Medication Adherence in Kidney Transplant Recipients

Introduction Medication non-adherence has been recognized as a great challenge in transplant center worldwide. Non-adherence to an immunosuppressive regimen has been reported to be associated with graft function loss and patient mortality. Medication adherence can be monitored directly through blood or urine drug assays, use of drug markers with the target medication, and observation of the patient ingesting the medication, or indirectly through patient self report, electronic monitoring device use, and prescription. Aim The aim of the study is examine efficacy and effectiveness of different assessment measurement methods and different self reported scales on medical adherence in kidney transplant recipient. Materials and Method This is cross-sectional and descriptive study was performed on 147 kidney transplant recipients. This study was conducting between April-November 2017. Data were collecting using Immunosuppressant therapy adherence scale-ITAS, Immunosuppressive Medication Adherence Scale (IMAS), biological assay assessment. For biological assay, last five tacrolimus blood plasma levels were evaluated and Standard Deviation (SD) was calculated for each patient. Medication non-adherence as SD cutt-off point was taken >2.58. Data were analyzed using SPSS software. Descriptive statistical analysis (mean, standard deviation, ratio). Written consent was obtained from all participants prior to data collection. Approval was given by the hospital and Ethics Committees. Results The mean age of the participants was 45.00±12.60 (min-max = 19-77y). Of the patients, 58.5% (n = 86) were male, 50.3% (n=74) were 10 year above after transplantation. It is determined 76 patients of 147 patients were used tacrolimus based immunosuppressive therapy. Tacrolimus levels of three patients were not reliable. Medication adherence SD level of 63% (n=59) was found under 2.58 and 22.37% (n= 15) of them was found elevated 2.58. ITAS mean is found 11.17±1.22 (min-max=4-12). In patients who only tacrolimus based therapy used, the mean total score obtained from the ITAS was 11.02±1.27 and 43, 18, 11 patients had taken full point, 11 and 10 point respectively. IMAS mean was found 43.42±3.46 (min-max=35-53). In patients who only tacrolimus based therapy used, the mean obtained from IMAS was 43.96±3.85. Conclusion We found that especially patient gave more higher in ITAS self reported assessment. Patient self-report is inadequate because patients tend to tell health care providers what they think the provider wants to hear. Also, the biological assay method may need careful interpretation, however, due to variations in pharmacokinetics. Electronic monitoring can be help to record pill-bottle cap opening data and time to reveal patients’ medication use. Thus, it has been suggested as a reference standard that assures the validity of adherence measurement. We advise to use electronic monitoring for assess to medication adherence of the patients.

WHAT IS THE EVIDENCE FOR THE ROLE OF THERAPEUTIC APHERESIS IN THE MANAGEMENT OF COMPLEMENT-ASSOCIATED THROMBOTIC MICROANGIOPATHIES?

Thrombotic microangiopathies (TMAs) are disorders characterized by endothelial cell activation, microangiopathic hemolytic anemia, thrombocytopenia and organ failure of variable intensity. The pathophysiology of various types of TMAs have become an interesting field of study. Alternative complement system activation plays an important role in several pathophysiological conditions. Complement activation is also described in an increasing number of TMAs. Inherited defects in complement regulatory genes and acquired autoantibodies against complement regulatory proteins have been described. Atypical hemolytic uremic synrome (HUS) is caused by uncontrolled activation of the alternative complement system, now called complement-mediated TMAs. Recently, application of a monoclonal antibody that specifically binds to C5 became available to treat patients with complement-mediated TMAs. Eculizumab is a humanized monoclonal antibody that blocks complement C5 activation. Empiric therapeutic apheresis is also recommended in all forms of complement-mediated TMAs. The justification for therapeutic apheresis use in all forms of complement-mediated TMAs is that it can effectively remove the autoantibodies or mutated circulating complement regulators while replacing absent or defective complement regulators. Currently, therapeutic apheresis and eculizumab are the available treatment options for complement-mediated TMAs. In this paper, we review the evidence for the role of therapeutic apheresis in the management of complement-associated TMAs.

Birincil Membranöz Nefropatide C4d Varlığı ve Yoğunluğunun Böbrek Hasarlanma Derecesi ile Birlikteliği

OBJECTIvE: The aim of this study was to evaluate the correlation between glomerular C4d staining and the demographic, clinical and histopathological findings in patients with primary membranous nephropathy (MN). MATErIAl and METhOdS: A total of 20 patients who underwent kidney biopsy and diagnosed as MN between 2005 and 2014 were included in this study. Patients were divided into two groups based on to C4d staining degrees and patterns. Those two groups were compared according to their demographical features, clinical follow-up, laboratory follow-up and histopathological findings. rESulTS: The percentage of segmental sclerosis (p=0.017), deposition of immunoglobulin A (p=0.044), and kappa and lambda proteins (p=0.029, p=0.049 respectively) were associated significantly with the negative-mild degree C4d staining group. Staining in a global pattern was statistically associated with intermediate-severe degree of C4d staining (p=0.001). The C4d staining patterns of the patients were then scored (segmental pattern one point, global pattern two point) and multiplied by the degree of C4d staining. The score of segmental/global pattern of staining factor was significantly higher within the intermediate-severe degree of C4d staining group (p<0.01). CONCluSION: Association of the global pattern and intermediate-severe degree of C4d staining suggests that immune deposition is more prevalent within the global pattern in primary MN. kEY wOrdS: C4d, Membranous nephropathy, Kidney injury