Background and Aims The great phenotypic heterogeneity in the presentation of kidney diseases makes the diagnostic strategy all the more complex in the elderly. While kidney biopsy should play a pivotal role, its non-negligible risk of bleeding complications (2-5% in the general population) justifies a certain reluctance to its application in the elderly. To date, however, there is little data on the benefit-risk ratio of kidney biopsy in the elderly. Most of these studies have focused on a relatively young population (60-70 years old) and on a limited number of patients. Concerning patients aged 80 years and older, very few studies have described the real therapeutic influence of kidney biopsy findings with regard to the rate of complications. Moreover, none of these studies have evaluated the long-term prognostic impact of therapeutic changes induced by the results of the kidney biopsy. The main objectives of this study are to describe the indications, diagnoses, complication rate, therapeutic influence and the prognostic impact of a change in therapeutic management after native kidney biopsies performed in patients aged 80 years and older. Method The KB-Old study (Kidney Biopsy for Old) is a retrospective multicenter cohort that consecutively included all patients aged 80 years and older who underwent percutaneous native kidney biopsy in 17 centers in the northern region of France, between 2010 and 2020. Clinical, biological and anatomopathological data as well as post-biopsy follow-up (therapeutic strategy, occurrence of complications) were collected from medical records. All pathology examinations were analyzed centrally by a team of experienced nephropathologists. Events of death or kidney failure were identified by specific registry cross-linking. To analyze the prognostic impact of therapeutic management following kidney biopsy (either initiation of a specific treatment or simple nephroprotection) on the risk of kidney failure and death, we performed Cox models weighted by propensity score (Inverse Probability of Treatment Weighting -IPTW-) in the population potentially eligible for treatment (exclusion of diseases without specific treatment). The areas under Kaplan Meier curves were calculated up to 6 years of follow-up (Restricted Mean Survival Time - RMST) and compared according to the initiation of a specific treatment after the kidney biopsy. This study was approved by Institutional Review Board (#AUG-20-707). Results Overall, the cohort included 453 patients (54% men, median age 83 years), half of whom underwent biopsy in the context of acute kidney injury (median serum creatinine level 3.0 mg/dl). The main diagnoses were nephroangiosclerosis (15%), renal involvement of hematological malignancies (13%), acute tubulointerstitial nephritis (12%) and vasculitis (10%). The complication rate was approximately 10%, with only 2.8% of serious complications requiring therapeutic intervention (mostly transfusion). The kidney biopsy identified a disease potentially accessible to a specific treatment in 73% of cases. After exclusion of patients with ineligible diseases, a specific treatment was initiated in about one out of two cases (163/332, 49%). After weighting on propensity score, the two treatment groups were globally balanced. A beneficial effect of treatment on dialysis-free survival was observed (HR = 0.51 [0.28-0.92], p = 0.02), without any major influence on mortality (Figure 1). Over a 6-year follow-up period, there was a gain in dialysis-free survival in the treated group estimated by the delta RMST at +10.46 months [3.39 - 17.54] compared with the untreated group (p = 0.004), with no difference in overall life expectancy. Conclusion To the best of our knowledge, this is the largest multicenter cohort of patients aged 80 years and over who have undergone kidney biopsy. It seems to confirm the interest and safety of this examination for specific indications, and a potentially important benefit on the prognosis when it leads to an adapted therapeutic management.
Background and Aims Acquired thrombotic thrombocytopenic purpura (aTTP) is a thrombotic microangiopathy still nowadays associated with a high risk of death. Standards of care included at first the association of plasmatic exchanges, Rituximab and steroids. The emergence of Caplacizumab, a nanobody targeting the A1 receptor of Von Willebrand Factor (VWF), significantly changed the prognosis of the disease. Thrombocytopenia is frequent in HIV positive patients, and aTTP is frequently considered. Prevalence of HIV positive in aTTP patients ranges from less than 1% in western countries, up to more than 50% in African countries. The pathophysiology still remains partially understood, leading to the development of autoantibodies targeting the ADAMTS13 metalloprotease. For now, no specific recommendations are available, and standards of care consist in treating HIV positive patient the same as other aTTP patients. We present the first description of two HIV positive patients, successfully treated with caplacizumab. Method We report there two cases of black women, respectively aged 31 (Patient 1) and 52 years old (Patient 2), both positive for HIV for several years. The first one had stopped any antiviral treatment few months ago, and had a positive blood viral load of 110764 copies/ml. Her CD4+ rate was 30/mm3. The second one was under antiviral medication, with a negative viral load and a CD4+ rate of 295/mm3. Both were admitted in our department because of low platelet levels and hemolysis, associated with inflammatory triggers. Bacteriema for Streptococcus mitis was discovered on admission in Patient 1 and Patient 2, who had a long-term follow-up for Still disease, presented with a flare-up. Results Both patients had positive anti-ADAMTS13 autoantibodies (Patient 1: titer 42 UI/ml, Patient 2: 45 UI/ml), with undetectable ADAMTS-13 activities. They were treated with plasmatic exchanges until platelets levels reached over 150 G/L, steroids 1.5 mg/kg/j, Rituximab 375 mg/m2 at day 1, 4 and 8 and finally caplacizumab 10 mg before the 2nd plasmatic exchange and every day until the ADAMTS13 activity reached over 20%. Antiviral therapy and antibiotics were initiated in Patient 1 and antiviral therapy was maintained in Patient 2. The evolution was promptly favorable with normalization of platelets levels at Day 4 in Patient 1, and Day 15 in Patient 2. Patient 1 stopped caplacizumab at Day 12 and Patient 2 at day 17, when ADAMTS 13 reached over 20%. None of them relapsed after treatment, with a respective follow-up of 4 and 2 months. Conclusion Caplacizumab seems to be a safe and efficient treatment for aTTP in HIV positive patients.
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