Interest of therapeutic plasmapheresis in a chronic hemodialysis patient with severe bullous pemphigoid.

Bullous pemphigoid is the most common autoimmune blistering disease induced by autoantibodies against basement membrane anchoring proteins (anti-BP-180 and anti-BP-230). The disease generally appears after the age of 70 and is associated with a 23.5% 1-year mortality, especially in diabetics, or in the presence of ischemic heart disease and high anti-BP-180. Treatment starts with topical steroids but some patients may require oral steroids and systemic immunosuppression. We, hereby, discuss a diabetic patient on chronic hemodialysis, with severely relapsed bullous pemphigoid under biotherapy with omalizumab, who was successfully treated with five sessions of double filtration plasmapheresis, thus avoiding the need for systemic steroids.

Anti-GBM antibody in a patient with diabetic nephropathy; all that glitters is not gold.

We present the case of a 58-year-old male diabetic patient admitted to our department for a slight decrease in kidney function, with nephrotic range proteinuria, hematuria (16,000/ml) and positive anti-glomerular basement membrane antibodies. Kidney biopsy revealed diabetic nephropathy with no evidence of crescent formation or linear immunoglobulin deposits along the basement membrane. We discuss the various clinical settings involving positive anti-glomerular basement membrane in the absence of crescentic glomerulonephritis.

Investigating the relationship between the number and activity of natural killer cells with increased cytomegalovirus and CMV disease after kidney transplantation.

BACKGROUND: Cytomegalovirus (CMV) infections caused by the cytomegalovirus are one of the most common problems in patients after kidney transplant. We examined the association of the relationship between the number and activity of natural killer cells with increased cytomegalovirus and its related disease after kidney transplantation. MATERIAL AND METHODS: In this analytical study, 58 new transplant patients in the Labbafinejad Hospital, who did not have any evidence of CMV infection, were evaluated based on the number and percentage of CD56+/16+, CD56+/16-, and CD69+ Natural Killer (NK) cells. RESULTS: The results of this study showed that CD16+ and CD56+ cells in the group of CMV Ag-positive patients are less than negative patients (p = 0.003) and the difference between the two groups are significant (p = 0.01). However, CD69+ cells did not differ significantly between the two groups (p = 0.1). Moreover, the absolute number of CD16+ and CD56+ cells declined significantly after infection with CMV unlike the CMV Ag - group(p = 0.003). DISCUSSION: These results indicate that kidney transplant patients suffering from CMV infection after transplantation have a significantly reduced total number of NK cells. On the other hand, a slight decrease in the number of NK subgroups was observed with an increase in the peak serum levels of cyclosporine. As a consequence of these findings, it can be assumed that more dosage and a higher level of the drug will result in more severe immunosuppression and, consequently, increased susceptibility to CMV infections. Thus, taking the right dose of the drug would prevent viral infections and immune system from over-activation.

Frequency of CD39+, LAG3+, and CTLA4+ Regulatory T Cells in Two Different Immunosuppressive Protocols in Renal Allograft Recipients (Sirolimus vs Mycophenolate mofetil): A Cohort Report.

BACKGROUND: Impaired renal function is considered as a significant risk factor for cardiovascular events in chronic kidney disease patients. Several immunosuppressive drugs are used in these patients, which necessitates to minimize the drug-related side effects by employing alternative strategies. OBJECTIVE: This study aimed to evaluate prospectively the influence of low dose ATG induction therapy with two different protocols (Sirolimus versus Mycophenolate mofetil) on the expression of functional markers (LAG-3, CD39, and intracellular CTLA-4) on conventional Tregs in renal recipients. METHODS: Thirty-eight renal transplant recipients were enrolled in this study. The patients were randomly assigned into two groups, including TMP: Tacrolimus (Tac), Mycophenolate mofetil (MMF), and Prednisolone (n=23); and TSP: Tac, Sirolimus (SRL), and Prednisolone (n=15). The frequency of LAG-3, CD39, and intracellular CTLA-4 on circulating Tregs was analyzed by flow cytometry before and after transplantation. RESULTS: Analysis of the flow cytometry data showed that the frequency of CD4+CD25+FOXP3+ Tregs increased 4 months post-transplantation compared to pre-transplantation in both groups, although this increase was only significant in TMP group. In TMP treated patients, the frequency of LAG-3+ Tregs and CD39+ Tregs increased, whereas the frequency of intracellular CTLA-4+ Tregs decreased 4 months post-transplantation. In TSP group, while the frequency of CD39+ Tregs increased, the frequency of CTLA-4+ Tregs decreased in post-transplantation compared to pre-transplantation. CONCLUSIONS: it seems that both treatment regimen protocols with a low dose ATG induction therapy may be clinically applicable in kidney transplant recipients.

Interest of a Kidney Biopsy to Rule out ANCA-Associated Renal Vasculitis in Glomerulonephritis Patients with a Positive ANCA.

Kidney biopsy is the gold standard for diagnosing glomerular kidney disease. Some authors debate the necessity of systematically performing kidney biopsies in ANCA-associated vasculitis (AAV) to confirm the diagnosis and assess the severity of renal damage. Nevertheless, kidney involvement is considered an organ-threatening disease requiring an aggressive immunosuppressive regimen. We present a series of 4 cases with a high clinical suspicion of ANCA-associated crescentic glomerulonephritis based on rising serum creatinine, presence of proteinuria and/or hematuria, and presence of ANCA with specificity against PR-3 or MPO. The main diagnosis, however, was arterionephrosclerosis without renal AAV. Certain comorbidities, such as diabetes and/or high blood pressure, can quickly mimic progressive glomerulonephritis. In addition, some patients with AAV do not have high creatinine, proteinuria, or hematuria levels. ANCA alone is not specific to AAV and has a poor positive predictive value. The main concern is to prevent the unnecessary, inappropriate complications of heavy immunosuppression, i.e., serious infections or risk of future malignancies. Kidney pathological confirmation is important in patients with no compatible extra-renal manifestations of AAV or any other possible renal diagnosis such as may be found in polyvascular disease or diabetic patients.

Characteristics of outpatients referred for a first consultation with a nephrologist: impact of different guidelines.

INTRODUCTION: Chronic kidney disease (CKD) affects > 10% of the population but not all CKD patients require referral to a nephrologist. Various recommendations for referral to nephrologists are proposed worldwide. We examined the profile of French patients consulting a nephrologist for the first time and compared these characteristics with the recommendations of the International Kidney Disease: Improving Global Outcomes (KDIGO), the French "Haute Autorité de Santé" (HAS), and the Canadian Kidney Failure Risk Equation (KFRE). METHODS: University Hospital electronic medical records were used to study patients referred for consultation with a nephrologist for the first time from 2016 to 2018. Patient characteristics (age, sex, diabetic status, estimated glomerular filtration rate (eGFR) and urine protein-to-creatinine ratio (PCR), etiology reported by the nephrologist) and 1-year patient follow-up were analyzed and compared with the KDIGO, HAS and Canadian-KFRE recommendations for referral to a nephrologist. The stages were defined according to the KDIGO classification, based upon kidney function and proteinuria.  RESULTS: The 1,547 included patients had a median age of 71 [61-79] years with 56% males and 37% with diabetes. The main nephropathies were vascular (40%) and glomerular (20%). The KDIGO classification revealed 30%, 47%, 19%, 4% stages G1-2 to G5, and 50%, 22%, 28% stages A1-A3, respectively. According to KDIGO, HAS and KFRE scores, nephrologist referral was indicated for 42%, 57% and 80% of patients respectively, with poor agreement between recommendations. Furthermore, we observed 890 (57%) patients with an eGFR> 30 ml/min and  a urine protein to creatinine ratio 0.5 g/g, mostly aged over 65 years (67%); 40% were diabetic, and 57% had a eGFR > 45 ml/min/1.73m2, 56% were diagnosed as vascular nephropathy and 11% with unknown nephropathy. CONCLUSION: These results underline the importance of better identifying patients for referral to a nephrologist and informing general practitioners. Other referral criteria (age and etiology of the nephropathy) are debatable.

The relationship between T-cell infiltration in biopsy proven acute T-cell mediated rejection with allograft function and response to therapy: A retrospective study.

AIM: To evaluate the degree of CD3, CD20, Th17, and Tregs infiltration in kidney biopsy of the patients with acute cellular rejection and the possible relation with graft outcome. MATERIALS AND METHODS: In this retrospective study, fifty patients with Acute T Cell-Mediated Rejection (ATCMR) were enrolled. Previous and one year clinical follow-up data were collected. The kidney specimens were evaluated for infiltration of CD3, CD20, FOXP3, and Th17 with IHC. According to the serum creatinine level in one-year follow-up of the patients after rejection therapy and function of the transplanted organ from the day admitted into the hospital, they were respectively categorized in Stable graft function versus impaired graft function; appropriate response to treatment versus failure to response. RESULTS: Treg (P = 0.96) and Th17 (P = 0.24) cells were more in the unstable group than the stable group, but the difference wasn't significant. On the other hand, the FOXP3/Th17 ratio was higher in the stable group (P = 0.22). Moreover Treg (P = 0.1) and Th17 (P = 0.15) were higher in failure to response group, but FOXP3/Th17 was higher in proper response group (P = 0.8). CONCLUSION: From the results, it can be concluded that TH17 infiltration has a more significant effect on graft outcome and response to rejection therapy.

Prognostic Value of Blood Pressure Responsiveness in Hemodialysis for Cardiovascular Mortality, Development of A New Predictive Equation.

INTRODUCTION: Cardiovascular disease is considered as the main cause of mortality and morbidity in HD-patients and AS is a fundamental cause. This study was conducted to investigate whether intradialytic BP changes can use as a surrogate clinical marker. METHODS: Fifty-one patients on maintenance hemodialysis, for at least 12 hours per week, were included in a prospective cohort study. Intradialytic BP was measured using validated automated device. PWV was performed to assess Augmentation Index (AIx) as marker of arterial stiffness. All measurements were repeated in alive individuals after 5 years of follow-up. Patients with 5% reduction of intradialytic BP were considered as HD-responsive and Several statistical analyses were employed based on responsiveness to HD. RESULTS: After 5-year follow-up the findings demonstrated BP response to HD was an important and independent determinant of mortality (P < .05). Augmentation index (AIx) (P < .05), heart rate (P < .05), and calcium phosphate product (P < .05) as well as log PTH (P < .05) were significantly different between two responsive and non-responsive to HD. Pearson's Correlation studies revealed a significant relationship between the BP response to HD and heart rate (r = 0.4, P < .05), LVEF (r = -0.4, P < .05) and PTH (r = -0.3, P < .05). BP response to HD and log-PTH remained significant even after age and gender adjustment (P < .05). CONCLUSION: BP-response to HD can use as a clinical and surrogate marker of AS which is significantly associated with mortality and LVEF. Arterial stiffness and intradialytic BP can predict the changes in Ejection Fraction (EF). DOI: 10.52547/ijkd.6810.

Association of IL-15 and IP-10 Serum Levels with Cytomegalovirus Infection, CMV Viral Load and Cyclosporine Level after Kidney Transplantation.

BACKGROUND: Cytomegalovirus (CMV) infection is the most common complications following kidney transplantation. Natural killer (NK) cells demonstrated critical anti-viral role in controlling and elimination of CMV after transplantation. Interleukin-15 (IL-15) is a pleiotropic cytokine that promotes the activity of NK cells and strengthens the acquired immune system. Also, IP10 (CXCL10) is a chemotactic factor which regulates NK cell recruitment and antiviral immune response. We aimed to determine the correlation between the serum levels of IL-15 and IP-10 cytokines with CMV infection, CMV viral load, and cyclosporine as a major immunosuppressive treatment after transplantation. METHODS: Fifty-eight kidney transplant recipient patients without evidence of CMV virus disease before transplantation surgery were included in the study. From the day of transplant surgery, the patients were evaluated based on the presence of CMV Ag pp65, CMV viral load, serum levels of IL-15 & IP-10, Cyclosporine levels (C0 & C2), Glomerular Filtration Rate (GFR), and hematological & biochemical Index, up to 75 days. RESULTS: Comparison analysis of serum levels of IL-15 and IP-10 showed no significant association with CMV infection in kidney transplant recipients. In addition, CMV viral load and cyclosporine levels at C0 and C2 did not affect patients' IL-15 and IP-10 levels. CONCLUSION: The levels of IP-10 and IL-15 cytokines are not affected with CMV infection, even if a viral infection occurs in the early days after transplantation or long afterwards. In addition, taking the different levels of cyclosporine did not affect the cytokines levels. Other mechanisms may play a role in maintaining the levels of these cytokines.

Humanized anti CD-20 as an alternative in chronic management of relapsing thrombotic thrombocytopenic microangiopathy resistant to rituximab due to anti chimeric antibody.

Acquired Immune thrombotic thrombocytopenic purpura (iTTP) is considered among clinical situations that needs not only urgent treatment in acute setting but also long term management to prevent relapses. Important progresses have been made in management of these patients that are definitely associated with reduced mortality and relapse rate. However, there are still noticeable percentage of patients that may relapse despite application of modern treatment strategies including preemptive rituximab infusions. Hereby, we share our experience concerning a frequently relapsing iTTP due to development of anti-rituximab antibody. In our case administration of obinutuzumab, a humanized type II anti CD-20 antibody was associated with complete peripheral blood B cell depletion and increasing plasma ADAMTS-13 activity.

Physiological role of plasma and its components and the clinical implications of different methods of apheresis: A narrative review.

Nowadays, therapeutic plasmapheresis (TP) is accepted as part of the treatment for specific groups of diseases. The availability of different methods, including double filtration and adsorption, increases selectivity for the removal of substances. However, the use of these techniques requires a thorough understanding of the characteristics and components of plasma. By considering pivotal papers from several databases, the aim of this narrative review is to describe the characteristics of plasma related to apheresis techniques. We have tried to cover the clinical implications including physiology, estimation of plasma volume, viscosity, and a description of its components including the size, volume of distribution, and half-lives of the different substances to be removed or maintained depending on the clinical situation and applied apheresis technique. Applying this knowledge will help us to choose the right method and dosage and improve the efficacy of the procedure by preventing or addressing any complications.

Impact of Circulating SARS-CoV-2 Mutant G614 on the COVID-19 Pandemic.

Coronavirus family has caused several human illnesses, the latest caused by SARS-CoV-2, has led to COVID-19 pandemic posing serious threat to global health. A SARS-CoV-2 variant encoding a D614G mutation in the viral spike (S) protein has now become the most prevalent form of the virus worldwide, suggesting a fitness advantage for the mutant. The G614 variant is associated with higher upper respiratory tract viral load, higher infectivity, increased total S protein incorporation into the virion, reduced S1 shedding and a conformational change leading to a more ACE2- binding and fusion- competent state. However, it does not seem to be correlated to increased disease severity or escape neutralizing antibodies.

Time-Varying Covariates and Risk Factors for Graft Loss in Kidney Transplantation.

OBJECTIVES: The present study was designed to evaluate the factors involved in long-term graft survival in recipients of kidney transplantation. MATERIALS AND METHODS: We reviewed 755 Iranian adult recipients who underwent kidney transplantation at Shahid Labbafinejad Medical Center in Tehran, Iran. Patients were followed for 5 years after transplantation. The primary outcome was the time between transplantation and graft loss. Using Cox regression, we studied the effect of time-independent variables (recipients' age and sex, donors' age, and type of donor), time-dependent covariates (body mass index [BMI], systolic blood pressure, diastolic blood pressure, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels, proteinuria and serum creatinine level), and immunosuppressive drugs on graft loss 60 months after transplantation. The results are presented as the hazard ratio (HR) with 95% confidence intervals. RESULTS: Result from Cox proportional hazards model showed that the HR of graft loss was 1.62 (95% CI: 1.03-2.54) in cadaveric donor compared with living donor kidney recipients. The HR of graft loss for recipient age was 1.02 (95% CI: 1.002-1.030). Moreover, according to obtained results, the risk of losing functional transplant increased for each mg/dL rise in serum creatinine at least 9% and at most 40%. Our results also showed that 1 unit increase of BMI has at least a 2% and at most a 15% decremented effect on the hazard ratio of graft loss. CONCLUSIONS: Having lower levels of creatinine and receiving a kidney from a younger living donor were associated with a decreased risk of graft loss. Graft loss is more likely to occur in patients with lower BMI.

How the COVID-19 Overcomes the Battle? An Approach to Virus Structure.

Coronaviruses primarily cause zoonotic infections, however in the past few decades several interspecies transmissions have occurred, the last one by SARS-CoV-2, causing COVID-19 pandemic, posing serious threat to global health. The SARS-CoV-2 spike (S) protein plays an important role in viral attachment, fusion and entry. However, other structural and non-structural SARS-CoV-2 proteins are potential influencers in virus pathogenicity. Among these proteins; Orf3, Orf8, and Orf10 show the least homology to SARSCoV proteins and therefore should be further studied for their abilities to modulate antiviral and inflammatory responses. Here, we discuss how SARS-COV-2 interacts with our immune system.

COVID-19 Rapid Guideline in Kidney Transplant Recipients.

in the reports presented about COVID-19, patients receiving kidney transplantation have not been specifically studied and based on national flowchart, this population is classified as highrisk group, thus it is necessary to be aware of the step-by-step treatment approach of these patients. Suspicious cases included patients with a history of dry cough, chills or sore throat accompanying by shortness of breath with or without fever, patients with upper/lower respiratory symptoms with radiological manifestations as single or double-sided multilobular infiltrations on CT scan or plain chest radiography, any one that has a history of close contact with a definite COVID-19 case within the last 14 days, any one with a history of presence in COVID-19 epidemic regions within the last 14 days and patient with pneumonia that despite of proper treatment has an inappropriate clinical response and clinical condition becomes more severe in an unusual way or unexpectedly.

Microvasculature partial endothelial mesenchymal transition in early posttransplant biopsy with acute tubular necrosis identifies poor recovery renal allografts.

Acute tubular necrosis (ATN), a frequent histopathological feature in the early post-renal transplant biopsy, affects long-term graft function. Appropriate markers to identify patients at risk of no or incomplete recovery after delayed graft function are lacking. In this study, we first included 41 renal transplant patients whose biopsy for cause during the first month after transplantation showed ATN lesions. Using partial microvasculature endothelial (fascin, vimentin) and tubular epithelial (vimentin) to mesenchymal transition markers, detected by immunohistochemistry, we found a significant association between partial endothelial to mesenchymal transition and poor graft function recovery (Spearman's rho = -0.55, P = .0005). Transforming growth factor-ß1 was strongly expressed in these phenotypic changed endothelial cells. Extent of ATN was also correlated with short- and long-term graft dysfunction. However, the association of extensive ATN with long-term graft dysfunction (24 months posttransplant) was observed only in patients with partial endothelial to mesenchymal transition marker expression in their grafts (Spearman's rho = -0.64, P = .003), but not in those without. The association of partial endothelial to mesenchymal transition with worse renal graft outcome was confirmed on 34 other early biopsies with ATN from a second transplant center. Our results suggest that endothelial cell activation at the early phase of renal transplantation plays a detrimental role.

Use of double filtration plasmapheresis for the treatment of acquired thrombocytopenic thrombotic purpura.

Double filtration plasmapheresis (DFPP) could be an alternative method to simple plasma exchange plasmapheresis in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP). In a retrospective single center case series, we studied clinical presentation, management care, and prognosis of aTTP patients from our academic center treated with DFPP and IV infusion of fresh frozen plasma (FFP) between 2009 and 2018. Nine patients were included for 11 episodes. Median age was 38 years old (IQR 26-53) with 78% women. Six episodes (55%) required admission to the ICU, four of which required mechanical ventilation. Median FFP volume transfused was 35.2 mL/kg/d of session. Response was complete for nine episodes (82%). Four patients presented an early relapse, two a late relapse. Four patients died: one had an active untreated HCV infection, and two were over 80-year-old polymorbid patients. DFPP seems to be an efficient method of therapeutic plasmapheresis in TTP when combined with FFP transfusion and immunosuppressive treatments.