When to use steroid treatment for those patients with drug-induced acute interstitial nephritis?
¿CUÁNDO TRATAR CON ESTEROIDES A LOS PACIENTES CON NEFRITIS INTERSTICIAL AGUDA POR FÁRMACOS?
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"tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "95" "paginaFinal" => "98" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => " Grupo Madrileño de Nefritis Intersticiales, Ester González, Manuel Praga" "autores" => array:3 [ 0 => array:1 [ "apellidos" => "Grupo Madrileño de Nefritis Intersticiales" ] 1 => array:3 [ "nombre" => "Ester" "apellidos" => "González" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] 2 => array:3 [ "nombre" => "Manuel" "apellidos" => "Praga" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:3 [ "entidad" => "Servicio de Nefrologia, Hospital 12 de Octubre, Madrid, Madrid, España, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "¿CUÁNDO TRATAR CON ESTEROIDES A LOS PACIENTES CON NEFRITIS INTERSTICIAL AGUDA POR FÁRMACOS?" ] ] "textoCompleto" => "<p class="elsevierStylePara">Drug-Induced Acute Interstitial Nephritis (DIAIN) represents a high percentage of acute renal failure in clinical practice.<span class="elsevierStyleSup">1,2</span> Some studies indicate that around 15% of biopsies with acute renal failure have DIAIN as the responsible injury for renal failure.<span class="elsevierStyleSup">3</span> To this, it must be added that many DIAIN cases are not biopsied and the diagnosis is based on clinical data and recent history of a new drug administration which as described below, sometimes is not so easy to identify. Although numerous drugs have been implicated, antibiotics and Non-steroidal Anti-inflammatory Drugs (NSAID) continue to be the drugs most involved.<span class="elsevierStyleSup">4</span> The etio-pathogenesis of the histological injury is well known and is produced by a mechanism of hypersensitivity to the drug. Even though this concept is well established, there is still some controversy as to the role of steroids in DIAIN treatment. While some studies have shown a positive steroid response in terms of a quicker and more complete renal function recovery in patients treated,<span class="elsevierStyleSup">5-7</span> other studies have not confirmed this steroid’s favorable outcome.<span class="elsevierStyleSup">8-11</span> The lack of factual information regarding therapeutic management of DIAIN is the result of limited data published to date: clinical cases and series which included very few patients.</p><p class="elsevierStylePara">The recent publication of a multicentre retrospective study, in which 10 Nephrology Departments in Madrid<span class="elsevierStyleSup">12</span> collaborated, has allowed not only the collection of the largest series published to date of biopsy proven DIAIN cases (61 patients), but also the publication of interesting findings on the influence of steroid treatment in this entity. As reflected in previous editorial comments,<span class="elsevierStyleSup">13</span> this collaborative study in Madrid has made an important contribution to the treatment of DIAIN.</p><p class="elsevierStylePara"><span class="elsevierStyleBold">NATURAL HISTORY OF DIAIN</span></p><p class="elsevierStylePara">The mechanism by which the kidney injury occurs is due to hypersensitivity to the drug which elicits a cellular immune response. This reaction causes an interstitial infiltration of T lymphocytes, monocytes, plasma cells, and eosinophils, and at the systemic level, the appearance of cutaneous rash, arthralgia fever, eosinophilia, and occasionally, an increase in hepatic enzymes. In addition to this, in the sediment eosinophiluria can appear as a result of the tubulo-interstitial inflammatory injury. In most of the cases, this kidney injury leads to acute renal failure, and although it is generally nonoliguric, it can be serious and require replacement therapy with haemodialysis.</p><p class="elsevierStylePara">Obviously, the first therapeutic step for a patient diagnosed with DIAIN should be identification of the causative agent and its immediate withdrawal. However, even though this first step seems evident, it is not that simple in clinical practice as in a great number of cases, particularly in elderly patients receiving multiple medications, identifying the drug responsible for DIAIN can be difficult and even impossible. It should be taken into account that, even though antibiotics and NSAIDs represent the majority of responsible drugs, any medication can cause DIAIN. Often the identification of the drug is based on an inquiry into the drug(s) more chronologically related to the appearance of DIAIN. We are often confronted with unreliable patients, particularly the elderly receiving multiple medicines, and the lack of clinical studies related to the interval between the start of treatment with a drug and the development of DIAIN. A good example of the difficulty encountered in the identification of the causal medicine is found in many cases of DIAIN secondary to NSAID intake. The consumption of these drugs by the general public is very widespread and these are often taken or prescribed in an intermittent way. They are found in many different presentations and a lot of patients are reluctant to admit their consumption.</p><p class="elsevierStylePara">Once the causal agent has been identified and withdrawn, if possible, there are unresolved issues for which we have very little information: What occurs to the characteristic interstitial infiltrate of DIAIN? How long does it take to be resolved? Does the parenchyma return to its original integrity or is it transformed into fibrotic scars? All of these questions are of considerable clinical importance, but there are no studies to clarify them.</p><p class="elsevierStylePara"><span class="elsevierStyleBold">EARLY STEROID TREATMENT CHANGES THE NATURAL COURSE OF DIAIN</span></p><p class="elsevierStylePara">The role of steroid treatment for DIAIN has caused controversy. Diverse clinical cases and series of patients (with a small number of patients) suggested that steroids are favourable, and renal function recovery is accelerated.<span class="elsevierStyleSup">5-7</span> Based on published reports, most authors have recommended steroid use with DIAIN only in patients with no evidence of renal function recovery after a 7-15 days observation period since suspension of the involved drug. However, there are many studies showing that a significant proportion of patients who suffer from a DIAIN do not completely recover their baseline renal function, remaining with different degrees of chronic renal failure after the acute injury.<span class="elsevierStyleSup">8-10</span></p><p class="elsevierStylePara">On the other hand, a recent retrospective study including a significant number of cases incited serious doubts over the validity of steroids in DIAIN.<span class="elsevierStyleSup">10</span> Out of the 60 patients with acute interstitial nephritis included in the study, 90% had DIAIN and non-steroidal anti-inflammatory drugs was the most frequent aetiology in 44% of cases. In this study, there were no differences in final creatinine levels among those patients who received steroids and those managed conservatively. However, close inspection reveals that steroid treatment began late, and although there are not significant differences between the group receiving steroids and those managed conservatively, various patients in both groups had good renal function improvement initially, but later they develop a degree of renal failure. This is an aspect which, in our opinion, has received very little attention in the literature: the majority of patients diagnosed with DIAIN show a noticeable improvement in renal function after suspending the causal drug. However, in many cases such an improvement tends to be interrupted before the patient can recover his/her baseline renal function ad integrum. Therefore, a considerable percentage of acute renal failure due to DIAIN develops into chronic renal failure with various degrees of severity. In the experience of the authors, it is not exceptional to find clear undiagnosed antecedents of DIAIN (such as acute deterioration of renal function accompanied by fever and eosinophilia after receiving antibiotics during hospitalization) in patients referred for chronic renal failure assessment.</p><p class="elsevierStylePara">Taking into account all of these unresolved issues, there is no doubt that the recently published collaborative study of the Madrid group<span class="elsevierStyleSup">12</span> has meant a new undertaking with important implications for clinical practice in DIAIN treatment.<span class="elsevierStyleSup">13</span> The study, which includes the most ample series published to date, is a retrospective analysis of 61 patients diagnosed with DIAIN through biopsy in 10 hospitals from the Community of Madrid during the period of 1975-2006. As in most of the series, antibiotics and NSAID were the main drugs involved, affecting 93% of patients. Although the study was retrospective, all patients had a baseline creatinine (1.1 ± 0.39mg/dl) measurement obtained 7.5 ± 4.6 months before the DIAIN diagnosis, and all patients had an extended follow-up, in such a way that the final renal function in each patient could be verified.</p><p class="elsevierStylePara">Analysing the small number of patients not treated with steroids (9 out of 61), a noteworthy difference stood out: at the end of the follow-up, they had significantly higher creatinine (3.71 ± 2.91 vs. 2.1 ± 2.1) and an incidence of chronic dialysis (44.4 vs. 3.8%) higher than the patients who received steroids. Additionally, the long-term follow-up of all patients and the availability of baseline creatinine allowed for a separation of the patients: those with complete baseline renal function recovery and those with chronic renal failure of variable severity. The most conclusive difference between both groups was the time interval between the withdrawal of the drug and the start of steroid treatment: 13 ± 10 days in the first group and 34 ± 17 days in the second. Furthermore, a significant correlation was found between the delay in the initiation of the steroids and final creatinine achieved. A time interval greater than seven days between the suspension of the drug and the start of steroid treatment was the only clinical factor of significant value in the multivariate analysis which increased the risk of incomplete renal function recovery.</p><p class="elsevierStylePara">The development of histological injuries also shows the convenience of early steroid treatment with DIAIN.<span class="elsevierStyleSup">12</span> All cases treated with steroids were administered after doing a renal biopsy, both in those which recovered renal function ad integrum and those that partially recovered. Therefore, in this study, an influence of previous steroid treatment could be ruled out in the histological findings. It was observed that in the cases with a long interval between the withdrawal of the causal medication and the biopsy, ample zones of interstitial fibrosis appeared; in contrast with the cases biopsied shortly after the withdrawal, in which cellular infiltrates were more predominant. In three cases a second renal biopsy was performed 33 ± 7 days after the first, due to unsuccessful development of renal function. One of these cases had only received conservative treatment, and the other two had received steroids very late after the suspension of the drug. In the three cases, a clear tubulo-interstitial fibrosis could be observed, which had mostly replaced the cellular infiltrates from the first biopsy. Collectively, all of this data point to the development of rapid interstitial fibrosis (in a few weeks) following characteristic interstitial infiltrates of DIAIN. Logically, the suspension of the drug is obligatory and results in a favourable effect, avoiding the continued formation of these cellular infiltrates. However, the steroid treatment allows a quick and efficient management of progressive and irreversible interstitial fibrosis development, which constitutes the histological base of chronic renal failure, as exhibited by the majority of non-treated cases or those treated late with steroids.</p><p class="elsevierStylePara">Some studies have suggested that DIAIN due to NSAID could have a worse development and prognosis, and a poor response to steroid treatment. We analysed the development of patients with DIAIN due to NSAID separately. Results were similar to the rest of the patients, showing that the delay in the initiation of the steroids was once again the most determining clinical factor in the incomplete recovery of baseline renal function. In patients with DIAIN due to NSAID, who recovered renal function ad integrum, after receiving steroid treatment, the treatment was started 18.4 ± 16 days after suspending the NSAID, a significantly shorter time interval as compared with the group that did not completely regain their renal function (31.4 ± 15 days).</p><p class="elsevierStylePara">Clearly the best and most robust way to define steroid treatment indications in DIAIN would be a randomized prospective study. However, as some authors have indicated, such study would not be viable due to its inherent difficulties.<span class="elsevierStyleSup">14</span> An important percentage of patients, in which DIAIN is suspected, are not Suitable for a biopsy due to underlying pathology or because they receive anti-platelet drugs or are anticoagulated, in which case the diagnosis is suspected by the clinical findings and by identifying the harmful drug. These cases of probable DIAIN, with a diagnosis based on clinical data, in the absence of a renal biopsy, constitute a substantial group in hospitals and often there is very little clinical information.<span class="elsevierStyleSup">15</span> Probably, the recommendations established in this document for DIAIN demonstrated by biopsy (withdrawal of the causing medicine and early steroid treatment) could also be applicable to this group of patients, but more clinical information is needed, even if it is with retrospectively analysed series.</p><p class="elsevierStylePara">Another aspect to point out in the collaborative study was the rare incidence of side effects due to steroids.<span class="elsevierStyleSup">12</span> This was probably due to the short duration of the treatment. Although the multicentre character of the study led to treatment criteria which differed from one centre to another, the mostly used schedule was pulsed steroid therapy (250-500mg of methyl prednisolone for 3-4 consecutive days) followed by oral prednisone (initial dosage 1mg/kg/day) that was progressively decreased and discontinued after 8-12 weeks.</p><p class="elsevierStylePara">To conclude, as previously reported, this study confirms DIAIN natural tendency to initial renal function improvement after the suspension of the drug involved. However, this initial improvement is frequently followed by progressive chronic renal failure (slow progression with terminal renal failure, greater risk of cardiovascular complications, etc.) The data supports the use of steroids in the treatment of all DIAIN and also its early administration. The analysis carried out in this study (regarding not only the timing of steroid therapy initiation but also whether or not the patient received steroids) gives a new insight into the long-term prognosis of acute renal failure due to DIAIN, since it shows that late commencement of steroid treatment leads to incomplete recovery of renal function in many cases, and that the earlier the treatment, is more likely to lead to complete recovery.</p><p class="elsevierStylePara"><span class="elsevierStyleBold">KEY CONCEPTS<br></br></span></p><p class="elsevierStylePara">1. Drug Associated Acute Interstitial Nephritis (DIAIN) represents a high percentage of acute renal failure in clinical practice.</p><p class="elsevierStylePara">2. Antibiotics and Non-steroidal Antiinflammatory Drugs (NSAID) are the most commonly implicated drugs in the development of DIAIN, although any medication can be responsible for this condition.</p><p class="elsevierStylePara">3. The kidney injury mechanism is due to hypersensitivity to the drug which stimulates a cell-mediated immune response. This reaction causes an interstitial infiltration of T lymphocytes, monocytes, plasma cells, and eosinophils.</p><p class="elsevierStylePara">4. When the responsible drug is suspended, a significant proportion of patients diagnosed with DIAIN do not completely recover their baseline renal function, remaining with different degrees of chronic renal failure after the acute injury.</p><p class="elsevierStylePara">5. The histological injury is characterized by acute cellular interstitial infiltrates that can be substituted rapidly (in a few weeks) by expanding tubulo-interstitial fibrosis.</p><p class="elsevierStylePara">6. In DIAIN, early establishment of steroid treatment ensures complete recovery of renal function while keeping the characteristic interstitial infiltrate from transforming progressively and irreversibly into fibrotic scars, which constitute the histological basis of chronic renal failure.</p>" "pdfFichero" => "P-E-S-A197-EN.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Rossert J. Drug-induced acute interstitial nephritis. Kidney Int 2001;60:804-17. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11473672" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Cameron JS. Allergic interstitial nephritis: clinical features and pathogenesis. Q J Med 1998;66:97-115. <a href="http://www.ncbi.nlm.nih.gov/pubmed/3051085" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Haas M, Spargo BH, Wit EJ, Meehan SM. Etiologies and outcome of acute renal insufficiency in older adults: a renal biopsy study of 259 cases. Am J Kidney Dis 2000;35:433-47. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10692269" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Baker RJ, Pusey CD. The changing profile of acute tubulointerstitial nephritis. Nephrol Dial Transplant 2004;19:8-11. <a href="http://www.ncbi.nlm.nih.gov/pubmed/14671029" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Galpin JE, Shinaberger JH, Stanley TM, et al. Acute interstitial nephritis due to methicillin. Am J Med 1978;65:756-65. <a href="http://www.ncbi.nlm.nih.gov/pubmed/707534" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Buysen JGM, Houtholf HJ, Krediet RT, Arisz L. Acute interstitial nephritis: a clinical and morphological study in 27 patients. Nephrol Dial Transplant 1990;5:94-9. <a href="http://www.ncbi.nlm.nih.gov/pubmed/2113219" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Pusey CD, Saltissi D, Bloodworth L, et al. Drug associated acute interstitial nephritis: clinical and pathological features and the response to high dose seteroid therapy. Q J Med 1983;52:194-211. <a href="http://www.ncbi.nlm.nih.gov/pubmed/6604293" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 7 => array:3 [ "identificador" => "bib8" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Bhaumik SK, Kher V, Arora P, et al. Evaluation of clinical and histological prognostic markers in drug-induced acute interstitial nephritis Ren Fail 1996;18:97-104. <a href="http://www.ncbi.nlm.nih.gov/pubmed/8820506" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 8 => array:3 [ "identificador" => "bib9" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Koselj M, Kveder R, Bren AF, Rott T. Acute renal failure in patients with drug-induced acute interstitial nephritis. Ren Fail 1993;15:69-72. <a href="http://www.ncbi.nlm.nih.gov/pubmed/8441839" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 9 => array:3 [ "identificador" => "bib10" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Clarkson MR, Giblin l, O¿Connell FP, et al. Acute interstitial nephritis clinical features and response to corticosteroid therapy. Nephrol Dial Transplant 2004;19:2778-83. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15340098" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 10 => array:3 [ "identificador" => "bib11" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Porile Jl, Bakris GL, Garella S. Acute interstitial nephritis with glomerulopathy due to nonsteroidal anti-inflammatory agents: a review of its clinical spectrum and effects of steroid therapy. J Clin Pharmacol 1990;30:468-75. <a href="http://www.ncbi.nlm.nih.gov/pubmed/2189904" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 11 => array:3 [ "identificador" => "bib12" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "González E, Gutiérrez E, Galeano C, et al. Early steroid treatment improves the recovery of renal function in patients with drug-induced acute interstitial nephritis. Kidney Int 2008;73:940-6. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18185501" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 12 => array:3 [ "identificador" => "bib13" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Appel GB. The treatment of acute interstitial nephritis. More data at last. Kidney Int 2008;73:905-7. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18379525" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 13 => array:3 [ "identificador" => "bib14" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Coca SG, Perazella MA. Early steroid treatment for druginduced acute interstitial nephritis. Nat Clin Pract Nephrol 2008;4:298-9. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18398413" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 14 => array:3 [ "identificador" => "bib15" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Espejo B, Herrero JC, Torres A, et al. Nefritis intersticial inmunoalérgica vs ateroembolismo de colesterol. Características diferenciales. Nefrología 2003;23:125-30." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/20132514/0000002900000002/v0_201502091631/X2013251409004834/v0_201502091631/en/main.assets" "Apartado" => array:4 [ "identificador" => "35429" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Editorials" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/20132514/0000002900000002/v0_201502091631/X2013251409004834/v0_201502091631/en/P-E-S-A197-EN.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251409004834?idApp=UINPBA000064" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 11 | 4 | 15 |
| 2024 October | 117 | 37 | 154 |
| 2024 September | 137 | 38 | 175 |
| 2024 August | 160 | 62 | 222 |
| 2024 July | 136 | 22 | 158 |
| 2024 June | 215 | 50 | 265 |
| 2024 May | 145 | 37 | 182 |
| 2024 April | 101 | 36 | 137 |
| 2024 March | 80 | 27 | 107 |
| 2024 February | 96 | 40 | 136 |
| 2024 January | 124 | 32 | 156 |
| 2023 December | 115 | 28 | 143 |
| 2023 November | 118 | 32 | 150 |
| 2023 October | 151 | 36 | 187 |
| 2023 September | 149 | 33 | 182 |
| 2023 August | 125 | 19 | 144 |
| 2023 July | 125 | 31 | 156 |
| 2023 June | 95 | 55 | 150 |
| 2023 May | 93 | 56 | 149 |
| 2023 April | 77 | 16 | 93 |
| 2023 March | 77 | 19 | 96 |
| 2023 February | 86 | 29 | 115 |
| 2023 January | 147 | 20 | 167 |
| 2022 December | 105 | 36 | 141 |
| 2022 November | 101 | 34 | 135 |
| 2022 October | 107 | 35 | 142 |
| 2022 September | 94 | 23 | 117 |
| 2022 August | 109 | 48 | 157 |
| 2022 July | 77 | 44 | 121 |
| 2022 June | 89 | 25 | 114 |
| 2022 May | 100 | 44 | 144 |
| 2022 April | 117 | 48 | 165 |
| 2022 March | 124 | 53 | 177 |
| 2022 February | 136 | 68 | 204 |
| 2022 January | 172 | 32 | 204 |
| 2021 December | 140 | 42 | 182 |
| 2021 November | 137 | 40 | 177 |
| 2021 October | 196 | 41 | 237 |
| 2021 September | 128 | 38 | 166 |
| 2021 August | 124 | 33 | 157 |
| 2021 July | 134 | 41 | 175 |
| 2021 June | 119 | 26 | 145 |
| 2021 May | 173 | 41 | 214 |
| 2021 April | 351 | 67 | 418 |
| 2021 March | 203 | 18 | 221 |
| 2021 February | 197 | 21 | 218 |
| 2021 January | 164 | 17 | 181 |
| 2020 December | 139 | 10 | 149 |
| 2020 November | 140 | 22 | 162 |
| 2020 October | 153 | 22 | 175 |
| 2020 September | 146 | 10 | 156 |
| 2020 August | 141 | 16 | 157 |
| 2020 July | 126 | 12 | 138 |
| 2020 June | 101 | 8 | 109 |
| 2020 May | 101 | 11 | 112 |
| 2020 April | 122 | 15 | 137 |
| 2020 March | 119 | 23 | 142 |
| 2020 February | 115 | 12 | 127 |
| 2020 January | 160 | 19 | 179 |
| 2019 December | 171 | 16 | 187 |
| 2019 November | 144 | 14 | 158 |
| 2019 October | 109 | 11 | 120 |
| 2019 September | 115 | 12 | 127 |
| 2019 August | 93 | 26 | 119 |
| 2019 July | 122 | 15 | 137 |
| 2019 June | 111 | 10 | 121 |
| 2019 May | 147 | 15 | 162 |
| 2019 April | 187 | 19 | 206 |
| 2019 March | 111 | 26 | 137 |
| 2019 February | 61 | 16 | 77 |
| 2019 January | 89 | 12 | 101 |
| 2018 December | 145 | 36 | 181 |
| 2018 November | 140 | 16 | 156 |
| 2018 October | 138 | 13 | 151 |
| 2018 September | 155 | 16 | 171 |
| 2018 August | 120 | 11 | 131 |
| 2018 July | 75 | 7 | 82 |
| 2018 June | 91 | 13 | 104 |
| 2018 May | 106 | 12 | 118 |
| 2018 April | 88 | 4 | 92 |
| 2018 March | 87 | 5 | 92 |
| 2018 February | 55 | 4 | 59 |
| 2018 January | 84 | 7 | 91 |
| 2017 December | 71 | 7 | 78 |
| 2017 November | 66 | 8 | 74 |
| 2017 October | 70 | 6 | 76 |
| 2017 September | 76 | 11 | 87 |
| 2017 August | 70 | 6 | 76 |
| 2017 July | 83 | 10 | 93 |
| 2017 June | 61 | 11 | 72 |
| 2017 May | 82 | 21 | 103 |
| 2017 April | 64 | 16 | 80 |
| 2017 March | 46 | 7 | 53 |
| 2017 February | 52 | 5 | 57 |
| 2017 January | 48 | 11 | 59 |
| 2016 December | 85 | 6 | 91 |
| 2016 November | 90 | 7 | 97 |
| 2016 October | 94 | 6 | 100 |
| 2016 September | 152 | 4 | 156 |
| 2016 August | 229 | 4 | 233 |
| 2016 July | 136 | 6 | 142 |
| 2016 June | 107 | 0 | 107 |
| 2016 May | 108 | 0 | 108 |
| 2016 April | 107 | 0 | 107 |
| 2016 March | 99 | 0 | 99 |
| 2016 February | 95 | 0 | 95 |
| 2016 January | 101 | 0 | 101 |
| 2015 December | 122 | 0 | 122 |
| 2015 November | 84 | 0 | 84 |
| 2015 October | 72 | 0 | 72 |
| 2015 September | 65 | 0 | 65 |
| 2015 August | 75 | 0 | 75 |
| 2015 July | 52 | 0 | 52 |
| 2015 June | 32 | 0 | 32 |
| 2015 May | 55 | 0 | 55 |
| 2015 April | 5 | 0 | 5 |
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