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Background: Passenger lymphocyte syndrome (PLS) causes immune-mediated hemolysis in solid and bone marrow transplant recipients. Donor-derived antibodies against the recipient erythrocyte drive the pathogenesis. It is a rare entity in kidney transplantation, and most of the cases are self-limited. Case presentation: A 36-year-old woman presented with fatigue 13 days after living donor renal transplantation. The operation was uneventful, and she was discharged with normal graft functions on the 11th day of transplantation Findings were consistent with cold agglutinin disease at her admission. However, the cold agglutinin test was negative. Eventually, she was diagnosed with PLS. Refractory intravascular hemolysis and frank hemoglobinuria were also present in the patient. Hemolysis was resistant to steroids, intravenous immunoglobulin (IVIG), and Rituximab. Because of life-threatening anemia related to refractory PLS, mycophenolate and tacrolimus were interrupted. However, hemolysis persisted. Following that, immunoadsorption (IA) treatment was obtained. Unfortunately, graft loss occurred due to rejection despite the resolution of PLS after IA. Conclusion: PLS is a rare and usually self-limited entity. Our case was an atypical refractory PLS that resembled cold agglutinin disease. Also, frank hemoglobinuria was observed related to severe intravascular hemolysis. These features have not been described before in PLS, to the best of our knowledge. Additionally, IA treatment had never been reported in the literature for PLS, as far as we know. Treatment and management could be a challenge in refractory PLS. Rituximab, IVIG, and extracorporeal treatments could be beneficial. It should be borne in mind that refractory PLS can cause graft and patient loss. Resumen: Antecedentes: El síndrome de linfocitos pasajeros (PLS) causa hemólisis inmunomediada en receptores de trasplantes sólidos y de médula ósea. Los anticuerpos derivados del donante contra el eritrocito receptor impulsan la patogénesis. Es una entidad rara en el trasplante de riñón y la mayoría de los casos son autolimitados. Presentación del caso: Una mujer de 36 años presentó fatiga 13 días después del trasplante renal de donante vivo. La operación transcurrió sin incidentes y fue dada de alta con las funciones normales del injerto el día 11 del trasplante. Los hallazgos coincidían con la enfermedad por crioaglutininas en el momento de su ingreso. Sin embargo, la prueba de crioaglutininas fue negativa. Finalmente, le diagnosticaron PLS. La paciente también presentó hemólisis intravascular refractaria y hemoglobinuria franca. La hemólisis fue resistente a los esteroides, la inmunoglobulina intravenosa (IgIV) y el rituximab. Debido a la anemia potencialmente mortal relacionada con PLS refractario, se interrumpieron el micofenolato y el tacrolimus. Sin embargo, persistió la hemólisis. A continuación, se obtuvo el tratamiento de inmunoadsorción (IA). Desafortunadamente, la pérdida del injerto ocurrió debido al rechazo a pesar de la resolución de PLS después de la IA. Conclusión: El PLS es una entidad rara y generalmente autolimitada. Nuestro caso fue un PLS refractario atípico que se asemejaba a la enfermedad por crioaglutininas. Además, se observó hemoglobinuria franca relacionada con hemólisis intravascular grave. Estas características no se han descrito antes en PLS, según nuestro leal saber y entender. Además, el tratamiento IA nunca se había informado en la literatura para PLS, hasta donde sabemos. El tratamiento y el manejo podrían ser un desafío en PLS refractarios. El rituximab, la IgIV y los tratamientos extracorpóreos podrían ser beneficiosos. Debe tenerse en cuenta que los PLS refractarios pueden provocar la pérdida del injerto y del paciente.

Abstract Background The largest data on the epidemiology of primary glomerular diseases (PGDs) are obtained from the databases of countries or centers. Here, we present the extended results of the Primary Glomerular Diseases Study of the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) Working Group. Methods Data of patients who underwent renal biopsy and received the diagnosis of PGD were recorded in the database prepared for the study. A total of 4399 patients from 47 centers were evaluated between May 2009 and May 2019. The data obtained at the time of kidney biopsy were analyzed. After the exclusion of patients without light microscopy and immunofluorescence microscopy findings, a total of 3875 patients were included in the study. Results The mean age was 41.5 ± 14.9 years. 1690 patients were female (43.6%) and 2185 (56.3%) were male. Nephrotic syndrome was the most common biopsy indication (51.7%). This was followed by asymptomatic urinary abnormalities (18.3%) and nephritic syndrome (17.8%). The most common PGD was IgA nephropathy (25.7%) followed by membranous nephropathy (25.6%) and focal segmental glomerulosclerosis (21.9%). The mean total number of glomeruli per biopsy was 17 ± 10. The mean baseline systolic blood pressure was 130 ± 20 mmHg and diastolic blood pressure was 81 ± 12 mmHg. The median proteinuria, serum creatinine, estimated GFR, and mean albumin values were 3300 (IQR: 1467–6307) mg/day, 1.0 (IQR: 0.7–1.6) mg/dL, 82.9 (IQR: 47.0–113.0) mL/min and 3.2 ± 0.9 g/dL, respectively. Conclusions The distribution of PGDs in Turkey has become similar to that in other European countries. IgA nephropathy diagnosed via renal biopsy has become more prevalent compared to membranous nephropathy.

Background/Aims: We aimed to investigate the effects of glomerular IgM and C3 deposition on outcomes of adult patients with primary focal segmental glomerulosclerosis (FSGS). Methods: In this retrospective analysis, 86 consecutive adult patients with biopsy-proven primary FSGS were stratified into 3 groups according to their histopathological features: IgM– C3–, IgM+ C3–, and IgM+ C3+. Primary outcome was defined as at least a 50% reduction in baseline estimated glomerular filtration rate (eGFR) or development of kidney failure, while complete or partial remission rates were secondary outcomes. Results: Glomerular IgM deposits were found in 44 (51.1%) patients, 22 (25.5%) of which presented with accompanying C3 deposition. Patients in IgM+ C3+ group had higher level of proteinuria (5.6 g/24 h [3.77–8.5], p = 0.073), higher percentage of segmental glomerulosclerosis (20% [12.3–27.2], p = 0.001), and lower levels of eGFR (69 ± 37.2 mL/min/1.73 m2, p = 0.029) and serum albumin (2.71 ± 0.85 g/dL, p = 0.045) at the time of diagnosis. Despite 86.3% of patients in IgM+ C3+ group (19/22) received immunosuppressive treatment, the primary outcome was more common in patients in the IgM+ C3+ group compared with patients in IgM+ C3– and IgM– C3– groups (11 [50%] vs. 2 [9%] and 11 [26.1%] respectively [p = 0.010]). Complete or partial remission rates were lower in patients in the IgM+ C3+ group (5/22, 22.7%), as well (p = 0.043). Multivariate Cox regression analysis revealed that IgM and C3 co-deposition was an independent risk factor associated with primary outcome (hazard ratio 3.355, 95% CI 1.349–8.344, p = 0.009). Conclusions: Glomerular IgM and C3 co-deposition is a predictor of unfavorable renal outcomes in adult patients with primary FSGS.

Background/Aims: The aim of this study is to investigate the utility of clinical [age, gender, mean arterial pressure (MAP)] and laboratory parameters [eGFR, hemoglobin (Hgb), serum levels of creatinine, uric acid, albumin, proteinuria, hematuria] and also histopathological lesions (Oxford classification parameters, crescents, intensity and pattern of staining for C3, C1Q, IgA, IgG, IgM) as progression markers in patients with IgA Nephropathy (IgAN). Methods: A total of 111 IgAN patients with a follow-up period >1 year or who reached kidney failure [GFR category G5 chronic kidney disease (CKD)] Results: Mean follow-up period was 33±29 months. Thirty-seven (33.3%) patients progressed to kidney failure and 4 (3.6%) patients developed eGFR decline ≥50% from the baseline after a median of 23 and 65 months, respectively. In multivariate Cox regression analysis, baseline levels of Hgb (HR:0.782, 95% CI 0.559-0.973, p=0.037), serum uric acid (HR:1.293, 95% CI 1.023-1.621, p=0.046), eGFR (HR:0.966, 95% CI 0.947-0.984, p=0.004) and intensity of C3 staining (HR:1.550, 95% CI 1.198-1.976, p=0.049) predicted primary endpoint. Serum uric acid level was associated independently with T score (β=0.303, p=0.005) in patients with eGFR>30 ml/min/m2. Conclusions: Hyperuricemia and the deposition of C3 are independent risk factors for IgAN progression.

Background. Membranous nephropathy (MN) is a common cause of nephrotic syndrome. In most cases it is idiopathic, while it may also be secondary to many diseases. In this study, prevalence of H. pylori infection and the effects of H. pylori eradication on proteinuria levels were investigated. Methods. Thirty five patients with MN (19 male), 12 patients with IgA nephropathy (4 male) and 12 patients with focal segmental glomerulosclerosis (FSGS) (8 male) were studied. The presence of H. pylori antigen was investigated in renal tissues obtained by biopsy, and the effects of H. pylori eradication on proteinuria levels were investigated. Results. Immunohistochemistry with H. pylori antigen revealed no positive staining in the glomeruli of all patients. 19 patients (54%) with MN, 10 (83%) with IgA nephropathy and 4 (33%) with FSGS were positive for H. pylori stool antigen test (P=0.045). Patients with H. pylori infection were administered eradication therapy (lansoprazole, 30 mg twice daily, plus amoxicillin, 0.75 g twice daily, plus clarithromycin, 250 mg twice daily, for 14 days). Before the eradication therapy the mean proteinuria of patients with MN, IgA nephropathy and FSGS were 2.42 ± 3.24 g/day, 2.12 ± 1.63 g/day and 1.80 ± 1.32 g/day, respectively. Three months after eradication, baseline proteinuria levels of patients with MN significantly decreased to 1.26 ± 1.73 g/day (P=0.031). In all three groups there were no significant differences with regard to serum creatinine, albumin and C-reactive protein levels before and after eradication therapy. Conclusions. The eradication of H. pylori infection may be effective to reduce proteinuria in patients with MN, while spontaneous remission of MN could not be excluded in this patient cohort. This trial is registered with NCT00983034.

Abstract Background We evaluated the efficacy of different immunosuppressive regimens in patients with primary membranous nephropathy in a large national cohort. Methods In this registry study, 558 patients from 47 centers who were treated with at least one immunosuppressive agent and had adequate follow-up data were included. Primary outcome was defined as complete (CR) or partial remission (PR). Secondary composite outcome was at least a 50% reduction in estimated glomerular filtration (eGFR), initiation of kidney replacement therapies, development of stage 5 chronic kidney disease, or death. Results Median age at diagnosis was 48 (IQR: 37–57) years, and 358 (64.2%) were male. Patients were followed for a median of 24 (IQR: 12–60) months. Calcineurin inhibitors (CNIs) with or without glucocorticoids were the most commonly used regimen (43.4%), followed by glucocorticoids and cyclophosphamide (GC-CYC) (39.6%), glucocorticoid monotherapy (25.8%), and rituximab (RTX) (9.1%). Overall remission rate was 66.1% (CR 26.7%, PR 39.4%), and 59 (10.6%) patients reached secondary composite outcome. Multivariate logistic regression showed that baseline eGFR (OR 1.011, 95% CI: 1.003–1.019, p = 0.007), serum albumin (OR 1.682, 95% CI: 1.269–2.231, p

Background: Treatment using direct-acting antivirals provides high rates of sustained virologic response and a favorable safety profile for patients with chronic hepatitis C virus infection. However, data on the efficacy of direct-acting antivirals in kidney transplant recipients are still limited. Aims: To evaluate the safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination in kidney transplant recipients. Study Design: Retrospective, observational, single-center study. Methods: Data of 29 kidney transplant recipients who received a fixed-dose safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination for 12 or 24 weeks with or without ribavirin were analyzed. The primary outcome was SVR12, which was defined as undetectable HCV-RNA levels 12 weeks after the treatment. Secondary outcomes were graft function, proteinuria, and calcineurin inhibitor trough level variability. Results: The predominant hepatitis C virus genotype was 1b (n = 19, 65.6%). All patients achieved SVR12. No graft failures nor deaths were reported during the study period. Throughout and after the treatment, the levels of aspartate aminotransferase [21 (range: 18-29.5) to 16 (range: 14-20) U/l, p < 0.001] and alanine aminotransferase [22 (range: 15-34) to 14 (range: 12-17.5) U/l, p < 0.001] improved significantly, unlike bilirubin, hemoglobin, and platelet levels. Renal function remained stable. Dose adjustments for calcineurin inhibitors were required. Serious adverse events were not observed. Conclusion: Safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination was effective and safe in kidney transplant recipients with hepatitis C virus. However, cautious monitoring of trough levels of calcineurin inhibitorss is needed due to potential drug-drug interactions during the treatment episode.

Abstract: The dipeptide boronic acid analogue bortezomib as a potent and selective inhibitor of the proteasome is used for the treatment of plasma cell dyscrasias such as multiple myeloma (MM). Bortezomib may induce glomerular microangiopathy (GMA) with or without systemic thrombotic microangiopathy (TMA) in which vascular endothelial growth factor-nuclear factor (VEGF) -κ B pathway could be involved. MM itself can cause TMA but primarily at presentation. Case report: We present a case with GMA associated with clinical features supporting systemic TMA shortly after bortezomib. Case: A 54-year-old woman has been diagnosed as having POEMS syndrome. She had symmetric mild degree of peripheral neuropathy, scleroatrophic skin lesions, Raynaud's phenomenon, and retinopathy. IgG kappa type paraproteinemia with a monotypic increase of plasma cells and increased pulmonary artery pressure contributed to the diagnosis. Bortezomib based treatment was started. Methodology: At the 20th day she developed severe dyspnea. Bilateral pleural effusion and acute kidney failure with thrombocytopenia and microangiopathic hemolytic anemia were documented. Urgent steroid and plasmapheresis were started. ADAMTS13 level proved to be within normal and plasmapheresis did not contribute to improvement. She commenced on hemodialysis and kidney biopsy was decided. Light microscopy findings revealed glomerular capillary thrombus, basement membrane thickening and segmental Results: duplication. Hyperplastic arteriolar changes were present. No immune deposits were detected by immunofluorescence microscopy. Biopsy findings were diagnostic for thrombotic microangiopathy. The clinical picture deteriorated as sleepiness and confusion. Cranial imaging and cerebrospinal fluid analysis showed no abnormality. Eculizumab with off-label approval contributed to stabilization but no improvement. Conclusion: Conclusion: Proteasome inhibitors associated with TMA may be life-threatening along with organ dysfunction due to microangiopathy-related ischemia. Membrane attack complex (C5b-9) deposition was found on endothelial cells in culture exposed to plasma from patients during the acute phase of the disease which may point to complement blockade benefit.

Tuberculous mastitis is a rare presentation of tuberculosis, which is a major health problem in kidney transplant recipients due to its high incidence and prevalence, and difficulty in diagnosis as well as high risk of morbidity and mortality. In daily practice, physicians may frequently be led to a misdiagnosis such as breast carcinoma or abscess. We believe it is crucial for clinicians to recognize this important presentation of the disease. Therefore, we present a case of tuberculous mastitis in a kidney transplant recipient who was admitted with fever of unknown origin and successfully treated using standard anti-tuberculosis therapy without any complications.

Background. Accelerated atherosclerosis and vascular calcification are common in chronic haemodialysis (HD) patients. In this study, we aimed to investigate the relationship between left ventricular hypertrophy (LVH) in HD patients and atherosclerosis and vascular calcification measured by electron beam computed tomography (EBCT).Methods. In a cohort of 118 HD patients (52 male, 66 female, mean age: 4613 years), we measured biochemical parameters, including BUN, creatinine, albumin, haemoglobin, C-reactive protein and fibrinogen levels, and performed echocardiography, high-resolution B-mode carotid ultrasonography and EBCT in 85 of them. The degree of stenosis was measured at four different sites (communis, bulbus, interna and externa) in both carotid arteries. Carotid plaque scores were calculated by summing the degrees of stenosis measured at all locations.Results. LVH was detected in 89 of the patients (75%). Plaque-positive patients had higher left ventricular mass index (LVMI) than plaque-negative patients (17559 vs 14346?g/m2, P = 0.003). LVMI was correlated with systolic blood pressure (r = 0.62, P<0.001), pulse pressure (r = 0.58, P<0.001), haemoglobin levels (r = ?0.25, P = 0.008), carotid plaque score (r = 0.32, P = 0.001) and coronary (CACS) and aortic wall calcification score (AWCS) (r = 0.34, P = 0.002 and r = 0.43, P<0.001, respectively). Multiple linear regression analysis (model r = 0.76) showed the independent factors related to LVMI to be systolic blood pressure, pulse pressure, CACS and presence of carotid plaques.Conclusion. Extra-coronary atherosclerosis and vascular calcification are associated with LVH in HD patients. Whether the treatment of atherosclerosis or vascular calcification may cause regression of or even prevent LVH in HD patients remains to be seen. [ABSTRACT FROM AUTHOR]

Background. Coronary artery calcification scores (CACS) calculated by electron beam computed tomography (EBCT) have been correlated with atherosclerotic burden in the non-uraemic population. However, the validity of this test in chronic haemodialysis patients (HD) is currently uncertain. In the present cross-sectional study, associations between carotid atherosclerosis and coronary calcification in HD patients are investigated.Methods. We studied 79 chronic HD patients (39 male, 40 female; mean age, 4512 years). The mean time on HD was 6854 months (range, 6187 months). In these patients, we measured serum calcium, phosphorus, total cholesterol, cholesterol subgroups and iPTH levels. EBCT, echocardiography, and high-resolution B-mode carotid Doppler ultrasonography were also performed.Results. Plaque-positive HD patients had significantly higher CACS than plaque-negative patients (851199 vs 428185, meanSE, P?=?0.006). Coronary calcification scores were correlated with serum phosphorus (r?=?0.37; P?=?0.001). Only 8 of the 24 HD patients without coronary calcification had carotid plaques (33%), whereas 34 of the 53 patients with coronary calcification had carotid plaques (64%) (P?=?0.015). Carotid plaque scores were correlated with CACS (r?=?0.40; P?=?0.001). A stepwise linear regression (model r?=?0.72; P<0.001) revealed that CACS (log-transformed data of CACS) was associated with age (P<0.001), time on dialysis (P?=?0.004), serum phosphorus level (P?=?0.016) and carotid plaque scores (P?=?0.037).Conclusions. Atherosclerosis is independently associated with coronary artery calcification and with hyperphosphataemia in chronic HD patients. CACS appeared to be predictive of both coronary atherosclerosis and carotid atherosclerosis. [ABSTRACT FROM AUTHOR]