Usefulness of mycophenolate mofetil in Indian patients with C3 glomerulopathy

Abstract Background C3 glomerulopathy (C3G) is a heterogeneous disease caused by alternative complement pathway abnormalities without any standardized treatment. An immunosuppressive agent, mycophenolate mofetil (MMF), has been recently shown to be useful in treating C3G, mainly in studies from the west. We report the clinical outcome of 17 Indian C3G patients treated with MMF with or without steroids. Methods The clinical and histology details of the C3G patients treated with MMF for at least 6 months with a follow-up of at least 12 months were retrieved from the medical records of our center. Results The median serum creatinine and proteinuria at presentation were 0.8 mg/dL and 3.7 g/day, respectively, with the majority (88.2%) presenting as nephrotic syndrome. The mean dose of MMF was 1.65 (±0.56) g/day, and the median duration of MMF therapy was 18 months. Two-thirds (64%) of the patients responded to the treatment, with complete remission in 4 (23%) and partial remission in 7 (41%) (median time: 9 months). Three patients progressed to end-stage renal disease (ESRD) on follow-up. Of the three patients, one (33%) had an initial response in proteinuria to MMF but did not respond after a relapse and subsequently progressed to ESRD and two (67%) other patients were nonresponsive to MMF from the start of the therapy. Conclusion Despite a small sample size and lack of a control arm, this study describes the effectiveness of MMF in treating C3G patients from Asia and forms a basis for future randomized trials.

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MO136RELATIONSHIP BETWEEN UPCR AND EGFR IN C3 GLOMERULOPATHY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab092.0014 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Carla Nester ◽

Patrick Breheny ◽

Monica Hall ◽

Alan Charney ◽

Martin Lefkowitz ◽

...

Keyword(s):

Natural History ◽

Small Sample Size ◽

Continuous Variable ◽

Small Sample ◽

C3 Glomerulopathy ◽

University Of Iowa ◽

History Of ◽

Stage Renal Disease ◽

End Stage ◽

The Relationship

Abstract Background and Aims Considerable knowledge gaps exist in our understanding of the natural history of C3 glomerulopathy (C3G). Disease rarity, multiple nomenclature changes, and the inclusion of dissimilar cases in historical cohorts have precluded retrospective studies to define the natural course of C3G and identify risks for progression to kidney failure (end stage renal disease/ESRD). In the present analysis, we focus on C3G patients with native kidneys and examine the relationship between reductions in UPCR and disease progression as indicated by changes in eGFR. Method Patients included in this study were consented and enrolled in the University of Iowa C3G ReCom Registry, which was created in 2013. Beginning in 2017, complement activity and renal function data were collected prospectively at approximately 6-month intervals to define the natural history of C3G. Analyses were performed across 1-year periods of time (“spans”). To be included in a span, a patient had to meet the following criteria at the start of the 1-year period: native C3G, eGFR ≥30 mL/min/1.73 m2, UPCR ≥1 g/g and ≥12 years of age. An individual patient could be included in more than one span. Results Analyses were performed using 34 one-year spans for 24 patients who met inclusion criteria at the beginning of the 1-year span. Baseline characteristics for the 34 spans were: male, 59%; mean age, 22.7 years; mean eGFR, 83.1 ml/min/1.73m2; mean UPCR, 2.86 g/g; mean plasma C3, 75.1 mg/dL. Similar analyses using only the first 1-year span for each of the 24 patients produced results that were consistent with those generated using all 1-year spans. Limitations of this study include its small sample size and data variability due to its observational nature. Conclusion The findings of this observational study support the premise that reductions in proteinuria are associated with a more stable eGFR in native kidney C3G. Regression analyses using UPCR as a continuous variable demonstrate the relationship between reduction in UPCR and preservation of eGFR. This association was also observed using both change in eGFR by UPCR reduction subgroup and UPCR-eGFR categorical analyses.

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Contact Activation Inhibitor, AB023, in Heparin-Free Hemodialysis: Results of a Randomized Phase 2 Clinical Trial

Blood ◽

10.1182/blood.2021011725 ◽

2021 ◽

Author(s):

Christina U. Lorentz ◽

Erik I. Tucker ◽

Norah G. Verbout ◽

Joseph J Shatzel ◽

Sven R Olson ◽

...

Keyword(s):

Small Sample Size ◽

Chronic Hemodialysis ◽

Small Sample ◽

Phase 2 ◽

Contact Activation ◽

Dialysis Dose ◽

Double Blind ◽

Phase 2 Clinical Trial ◽

Stage Renal Disease ◽

End Stage

End-stage renal disease (ESRD) patients on chronic hemodialysis have repeated blood exposure to artificial surfaces that can trigger clot formation within the hemodialysis circuit. Dialyzer clotting can lead to anemia despite erythropoietin and iron supplementation. Unfractionated heparin prevents clotting during hemodialysis, but it is not tolerated by all patients. Although heparin-free dialysis is performed, intradialytic blood entrapment can be problematic. To address this issue, we performed a randomized, double-blind, phase 2 study comparing AB023, a unique antibody that binds factor (F) XI and blocks its activation by factor XIIa but not by thrombin, to placebo in 24 patients with ESRD undergoing heparin-free hemodialysis (www.clinicaltrials.gov #NCT03612856). Patients were randomized to receive a single pre-dialysis dose of AB023 (0.25 or 0.5 mg/kg) or placebo in a 2:1 ratio and safety and preliminary efficacy were compared to placebo and to observations made prior to dosing within each treatment arm. AB023 administration was not associated with impaired hemostasis or other drug-related adverse events. Occlusive events requiring hemodialysis circuit exchange were less frequent and levels of thrombin-antithrombin complexes and C-reactive protein were lower after AB023 administration compared with data collected prior to dosing. AB023 also reduced potassium and iron entrapment in the dialyzers, consistent with less blood accumulation within the dialyzers. We conclude that despite the small sample size, inhibition of contact activation-induced coagulation with AB023 was well tolerated and reduced clotting within the dialyzer.

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Endovascular mechanical thrombectomy and stenting in a case of central vein thrombosis

BMJ Case Reports ◽

10.1136/bcr-2020-236508 ◽

2021 ◽

Vol 14 (2) ◽

pp. e236508

Author(s):

Rajesh Vijayvergiya ◽

Navjyot Kaur ◽

Saroj K Sahoo ◽

Ashish Sharma

Keyword(s):

Mechanical Thrombectomy ◽

Transluminal Angioplasty ◽

Brachiocephalic Vein ◽

Central Vein ◽

Vein Thrombosis ◽

Catheter Directed Thrombolysis ◽

Stage Renal Disease ◽

End Stage ◽

Vein Stenosis

Central vein stenosis and thrombosis are frequent in patients on haemodialysis for end-stage renal disease. Its management includes anticoagulation, systemic or catheter-directed thrombolysis, mechanical thrombectomy and percutaneous transluminal angioplasty (PTA). Use of mechanical thrombectomy in central vein thrombosis has been scarcely reported. We hereby report a case of right brachiocephalic vein thrombosis with underlying stenosis, which was successfully treated by mechanical thrombectomy followed by PTA and stenting. The patient had a favourable 10 months of follow-up.

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Assessing Biomarkers of Breast Cancer Risk in Underserved Women in a Midwestern County

Journal of Primary Care & Community Health ◽

10.1177/21501327211017792 ◽

2021 ◽

Vol 12 ◽

pp. 215013272110177

Author(s):

Marla A. DeWitt ◽

Ivana T. Croghan ◽

Celine M. Vachon ◽

Thomas D. Thacher ◽

Marcia R. Venegas Pont ◽

...

Keyword(s):

Vitamin D ◽

Mammographic Density ◽

Small Sample Size ◽

Vitamin D Insufficiency ◽

Screening Mammography ◽

Small Sample ◽

Vitamin D Status ◽

Small Pilot Study ◽

Unexpected Findings

Objective: The primary aim of this study was to evaluate the feasibility of collecting risk factor information and accessing digitized mammographic data in a medically marginalized population. A secondary aim was to examine the association between vitamin D status and mammographic density. Methods: Breast-screening examinations were provided for age-appropriate patients, and a referral for no-cost screening mammography was offered. Study participants were asked to undergo 25-hydroxyvitamin D testing at mammography and 1-year follow-up. Results: Of 62 women approached, 35 (56%) consented to participate. Of 32 participants who had baseline mammography, the median mammographic density measured by VolparaDensity (Volpara Solutions Limited) was 5.7%. After 1 year, 9 women obtained follow-up mammograms, with a median density of 5.7%. Vitamin D status was measured for 31 participants at baseline and 13 participants in the following year. Insufficient vitamin D status (<30 ng/mL) was noted in 77% at each time point. Mammographic density was not significantly correlated with vitamin D status ( P = .06). Conclusions: On the basis of this small pilot study, vitamin D insufficiency is common in this study population. Owing to the small sample size, an association between vitamin D insufficiency and breast density was not clear. Additional unexpected findings included substantial barriers in initial access to care and longitudinal follow-up in this population. Further study of these issues is needed.

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Living Kidney Donation: Practical Considerations on Setting Up a Program

Transplantology ◽

10.3390/transplantology2010008 ◽

2021 ◽

Vol 2 (1) ◽

pp. 75-86

Author(s):

Maria Irene Bellini ◽

Vito Cantisani ◽

Augusto Lauro ◽

Vito D’Andrea

Keyword(s):

Good Practice ◽

Kidney Donation ◽

Living Kidney Donation ◽

Exchange Programs ◽

Paired Exchange ◽

Stage Renal Disease ◽

End Stage ◽

Additional Value ◽

Work Up

Living kidney donation represents the best treatment for end stage renal disease patients, with the potentiality to pre-emptively address kidney failure and significantly expand the organ pool. Unfortunately, there is still limited knowledge about this underutilized resource. The present review aims to describe the general principles for the establishment, organization, and oversight of a successful living kidney transplantation program, highlighting recommendation for good practice and the work up of donor selection, in view of potential short- and long-terms risks, as well as the additional value of kidney paired exchange programs. The need for donor registries is also discussed, as well as the importance of lifelong follow up.

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Vasculitis ANCA: Alternativas de tratamiento y las expectativas en los pacientes

Karger Kompass Neumología ◽

10.1159/000513798 ◽

2021 ◽

pp. 1-2

Author(s):

Carolina Aguilar-Martínez

Keyword(s):

Systematic Review ◽

Cox Regression ◽

Meta Analysis ◽

Significant Risk ◽

Limiting Factor ◽

Significant Survival ◽

Stage Renal Disease ◽

End Stage ◽

Immunosuppression Therapy

Background: The benefits of treating anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) in advancing age remains unclear with most published studies defining elderly as ≥65 years. This study aims to determine outcomes of induction immunosuppression in patients aged ≥75 years. Methods: A cohort of patients aged ≥75 years with a diagnosis of AAV between 2006 and 2018 was constructed from 2 centres. Follow-up was to 2 years or death. Analysis included multivariable Cox regression to compare mortality and end-stage renal disease (ESRD) based on receipt of induction immunosuppression therapy with either cyclophosphamide or rituximab. A systematic review of outcome studies was subsequently undertaken amongst this patient group through Pubmed, Cochrane and Embase databases from inception until October 16, 2019. Results: Sixty-seven patients were identified. Mean age was 79 ± 2.9 years and 82% (n = 55) received induction immunosuppression. Following systematic review, 4 studies were eligible for inclusion, yielding a combined total of 290 patients inclusive of our cohort. The aggregated 1-year mortality irrespective of treatment was 31% (95% CI 25–36%). Within our cohort, induction immunosuppression therapy was associated with a significantly lower 2-year mortality risk (hazard ratio [HR] 0.29 [95% CI 0.09–0.93]). The pooled HR by meta-analysis confirmed this with a significant risk reduction for death (HR 0.31 [95% CI 0.16–0.57], I2 = 0%). Treated patients had a lower pooled rate of ESRD, but was not statistically significant (HR 0.71 [95% CI 0.15–3.35]). Conclusion: This meta-analysis suggests that patients ≥75 years with AAV do benefit from induction immunosuppression with a significant survival benefit. Age alone should not be a limiting factor when considering treatment.

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Vascular access types in patients starting hemodialysis after failed kidney transplant: does close nephrology follow-up matter?

The Journal of Vascular Access ◽

10.5301/jva.5000631 ◽

2016 ◽

Vol 18 (1) ◽

pp. 22-25 ◽

Cited By ~ 3

Author(s):

Naveed Ul Haq ◽

Mohamed Said Abdelsalam ◽

Mohammed Mahdi Althaf ◽

Abdulrahman Ali Khormi ◽

Hassan Al Harbi ◽

...

Keyword(s):

Vascular Access ◽

Clinic Visit ◽

Study Data ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Early Referral ◽

Period Data ◽

Stage Renal Disease ◽

End Stage

Background Native arteriovenous fistulae (AVFs) are preferred while central venous catheters (CVCs) are least suitable vascular access (VA) in patients requiring hemodialysis (HD). Unfortunately, around 80% of patients start HD with CVCs. Late referral to nephrologist is thought to be a factor responsible for this. We retrospectively analyzed the types of VA at HD initiation in renal transplant recipients followed by nephrologists with failed transplant. If early referral to nephrologist improves AVF use, these patients should have higher prevalence of AVF at HD initiation. Methods All patients who failed their kidney transplants from January 2002 to April 2013 were included in the study. Data regarding planning of VA by nephrologist, documented discussion about renal replacement therapy (RRT), estimated glomerular filtration rate (eGFR) at 6 months and last clinic visit before HD initiation, time of VA referral, and subsequent VA at dialysis initiation were gathered and analyzed. Results Eighty-three patients failed their transplants during study period. Data were inaccessible in six patients. Eleven patients started peritoneal dialysis (PD) while 66 started HD. Thirty-two had previous functioning VA while 34 needed VA. There were 11/34 patients (32%) with eGFR <15 mL/min at six months while 21/34 (61%) had eGFR <15 mL/min at last clinic visit before HD initiation. Only 11/34 (32%) had documented RRT discussion, 8/34 (24%) had VA referral, and 7/34 (21%) had vein mapping. A total of 30/34 (88.3%) started HD with CVC while 4/34 (11.3%) started HD with AVF (p<0.0001). Conclusions Early referral to nephrologist by itself may not improve VA care amongst patient with end-stage renal disease.

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MO282EARLY RENAL RECOVERY AFTER A FIRST FLARE OF PAUCI IMMUNE GLOMERULONEPHRITIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab104.0040 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Jeremy Zaworski ◽

Cyrille Vandenbussche ◽

Pierre Bataille ◽

Eric Hachulla ◽

Francois Glowacki ◽

...

Keyword(s):

Renal Disease ◽

End Stage Renal Disease ◽

Interstitial Fibrosis ◽

Univariate Analysis ◽

Renal Recovery ◽

Neurological Involvement ◽

Factors Associated ◽

Stage Renal Disease ◽

End Stage

Abstract Background and Aims Renal involvement is a severe manifestation of ANCA-associated vasculitis. Patients often progress to end-stage renal disease. The potential for renal recovery after a first flare has seldom been studied. Our objectives were to describe the evolution of the estimated glomerular filtration rate (eGFR) and identify factors associated with the change in eGFR between diagnosis and follow-up at 3 months (ΔeGFRM0–M3) in a cohort of patients with a first flare of pauci-immune glomerulonephritis. Methods This was a retrospective study over the period 2003–2018 of incident patients in the Nord-Pas-de-Calais (France). Patients were recruited if they had a first histologically-proven flare of pauci immune glomerulonephritis with at least 1 year of follow up. Kidney function was estimated with MDRD-equation and analysed at diagnosis, 3rd, 6th and 12th months. The primary outcome was ΔeGFRM0–M3. Factors evaluated were histological (Berden classification, interstitial fibrosis, percentage of crescents), clinical (extra-renal manifestations, sex, age) or biological (severity of acute kidney injury, dialysis, ANCA subtype). Results One hundred and seventy-seven patients were included. The eGFR at 3 months was significantly higher than at diagnosis (mean ± standard deviation, 40 ± 24 vs 28 ± 26 ml/min/1.73 m2, p < 0.001), with a ΔeGFRM0–M3 of 12 ± 19 ml/min/1.73 m2. The eGFR at 12 months was higher than at 3 months (44 ± 13 vs 40 ± 24 ml/min/1.73m2, p = 0.003). The factors significantly associated with ΔeGFRM0–M3 in univariate analysis were: sclerotic class according to Berden classification, percentage of interstitial fibrosis, percentage of cellular crescents, acute tubular necrosis, neurological involvement. The factors associated with ΔeGFRM0–M3 in multivariate analysis were the percentage of cellular crescents and neurological involvement. The mean increase in eGFR was 2.90 ± 0.06 ml/min/1.73m2 for every 10-point gain in the percentage of cellular crescents. ΔeGFRM0–M3 was not associated with the risks of end-stage renal disease or death in long-term follow-up. Conclusions Early renal recovery after a first flare of pauci-immune glomerulonephritis occurred mainly in the first three months of treatment. The percentage of cellular crescents was the main independent predictor of early renal recovery.

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MO302ACUTE POST-INFECTIOUS GLOMERULONEPHRITIS IN ADULTS: A TUNISIAN SINGLE CENTER EXPERIENCE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab104.0060 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Imen El Meknassi ◽

Mrabet Sanda ◽

Guedri Yosra ◽

Zellema Dorsaf ◽

Azzabi Awatef ◽

...

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Acute Glomerulonephritis ◽

Industrialized Countries ◽

Single Center Experience ◽

Nephritic Syndrome ◽

Stage Renal Disease ◽

End Stage ◽

Post Infectious

Abstract Background and Aims Acute post-infectious glomerulonephritis (APIGN) is a reactive immunological disease. Its prevalence in industrialized countries is declining contrasting with developed ones. It is uncommon in adults but the prognosis may be reserved. The aim of our study was to evaluate the epidemiological, clinical and histological features of APIGN as well as its prognosis. Method A retrospective and descriptive study was conducted in our department. Were included all cases of histologically proven APIGN between December 2006 and December 2017. Results We had collected 38 cases. The mean age was 37.7 ± 17.8 years. The sex ratio was 1.92. Twelve (31.6%) patients were diabetic and four of them had already a chronic kidney disease (CKD). APIGN was preceded by an infection in 27 cases with an average interval of 10 ± 5 days. The most common site of infection was the respiratory tract (15 cases). At presentation, 27 patients had nephritic syndrome and 13 had nephrotic-range proteinuria. Hematuria was observed in 97.4%, peripheral edema in 84.2% and hypertension in 73.7% of cases. Most patients (78.9%) had acute kidney injury and 10 (26.3%) patients required dialysis. Renal biopsy had shown benign acute glomerulonephritis in 31 cases and malignant form in 7 cases. An underlying nephropathy was found in 12 cases with mostly a diabetic nephropathy. Corticosteroids were used in 3 cases of benign APIGN and 5 cases of malignant form. During the follow-up, CKD was noted in 14(36.8%) patients including 7(18.4%) patients who progressed to end-stage renal disease. Poor prognostic factors were diabetes, the presence of an underlying nephropathy in the biopsy, acute kidney injury and the need for dialysis. Conclusion The APIGN is uncommon in adults, yet its prognosis may be reserved with progression to CKD.

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Role of multiparametric MRI in long-term surveillance following focal laser ablation of prostate cancer

British Journal of Radiology ◽

10.1259/bjr.20210414 ◽

2021 ◽

pp. 20210414

Author(s):

Mark Paxton ◽

Eitan Barbalat ◽

Nathan Perlis ◽

Ravi J Menezes ◽

Mark Gertner ◽

...

Keyword(s):

Laser Ablation ◽

Recurrent Disease ◽

Small Sample Size ◽

Focal Therapy ◽

Outcome Data ◽

Small Sample ◽

Restricted Diffusion ◽

Treatment Site ◽

Imaging Characteristics

Objective: Determine the multiparametric magnetic resonance imaging (mpMRI) appearance of the prostate following focal laser ablation (FLA) for PCa and to identify imaging characteristics associated with recurrent disease. Methods: Retrospective analysis of patients who underwent FLA for low-intermediate risk PCa between 2010 and 2014 was performed. Early (median 4 months) and late mpMRI (median 49 months) follow-up were qualitatively assessed for T2-weighted, dynamic contrast enhanced (DCE) and diffusion weighted imaging (DWI) appearances and also compared to corresponding PSA values and biopsy results. Results: 55 cancers were treated in 54 men (mean age 61.0 years). Early mpMRI was performed in 30 (54.5%) patients while late follow-up mpMRI in 42 (84%). Ill-defined scarring with and without atrophy at the treatment site were the most common appearances. In patients with paired MRI and biopsy, one of four patients with clinically significant PCa on biopsy (≥GG2 or≥6 mm GG1) showed hyperenhancement or restricted diffusion at early follow-up. At late follow-up, positive biopsies were seen in 5/8 (63%) cases with hyperenhancement and 5/6 (83%) cases with restricted diffusion at the treatment site. PSA change was not associated with biopsy results at either time point. Conclusion: mpMRI is able to document the morphological and temporal changes following focal therapy. It has limited ability to detect recurrent disease in early months following treatment. Late-term mpMRI is sensitive at identifying patients with recurrent disease. Small sample size is, however, a limitation of the study. Advances in knowledge: Implementing MRI in follow-up after FT may be useful in predicting residual or recurrent PCa and therefore provide reliable outcome data.

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