PATIENT BENEFITS OF NEPHROLOGICAL FOLLOW-UP BEFORE THE INITIATION OF RRT-AN OBSERVATIONAL RETROSPECTIVE ANALYSIS

BACKGROUND AND AIMS: The clinical follow-up of CKD patients by nephrologists before RRT initiation (RRTi) is recommended by the practice guidelines starting with stage 3b CKD [1]. Despite this, the real-life implementation in clinical practice suggests otherwise, based on the paucity of papers reporting on the matter [2, 3]. In Romania, where the representation of the nephrology outpatient care is scarce, partly because of the low number of specialists, the establishment of outpatient clinics attached to dialysis units could be a solution. The purpose of this analysis is to evaluate, for the first time, if nephrological monitoring through the Diaverum outpatient clinics has benefits for CKD patients. METHOD: A total of 344 patients from 9 Diaverum clinics have been evaluated (335 haemodialysis, 9 peritoneal dialysis), our present analysis retaining only those starting haemodialysis, of which 118 started RRT in the 3 years between 1 January 2015 and 31 December 2017 and were monitored through the nephrology outpatient and 217 were patients there were not referred to a nephrology unit until RRTi, in the 2 years between 1 July 2016 and 1 July 2018. Clinical and laboratory data were gathered at RRTi and the follow up was investigated over a period of 3 years for both groups, starting from the end of the inclusion period, using anonymized records from the electronic database of Diaverum. Collected data were compared using the Pearson test for nominal variables and the Student's t-test and Wilcoxon Mann-Whitney U-tests for continuous variables. Survival analysis was employed using the Kaplan-Meier estimate and Cox regression models. RESULTS: The patient groups had similar general characteristics: most were men, >40% being elder (>65 yo), ∼30% had DM and both groups were comprised of subjects with multiple comorbidities (a mean Charlson score of 6). For patients that were not nephrologically referred, RRT was started in 100% of the cases using a CVC, while AVFs were employed in a majority of those followed through the outpatient clinics. In both groups, the mean eGFR was similarly <10 mL/min/1/73 m2, but >7 mL/min/1.73 m2, reflecting an alignment to clinical practice guidelines [1]. The median level of haemoglobin and the percentage of those with an optimal level of haemoglobin were higher in the group of monitored patients (9.9 versus 8.4 g/dL, respectively, 42% versus 15%).The nutrition status faired better in monitored patients: BMI (26 versus 23.3 kg/m2) and serum albumin (3.8 versus 3.5 g/dL). Serum calcium levels were higher (8.8 versus 8.3 mg/dL) and serum iPTH levels were lower (264 versus 331 pg/mL) in monitored patients, suggesting a better control of CKD-MBD, but serum phosphate was higher (5.7 versus 4.64 mg/dL), possibly reflecting a better nutrition status. The number of hospital admissions, COVID-19 cases and deaths are hard to compare, given the different observation periods that covered different periods and waves of the COVID-19 pandemic. However, hospital admissions and COVID-19 cases seemed more frequent in those that were not monitored. The 4 year survival rate was significantly higher (59% versus 51%) in the Kaplan- Meier analysis for those monitored through the outpatient. In the multivariate analysis, statistically significant associations with mortality were observed for diabetic and unmonitored patients. A major bias in our analysis is the difference between the periods of follow-up, which featured different periods of the COVID-19 pandemic. CONCLUSION: This is the first observational analysis on a nephrological patient population from Romania, which was followed through outpatient units until the initiation of RRT. Patient monitoring before RRTi potentially allows: for a better control of the main complications of CKD (anaemia, CKD-MBD), a better preparation for RRTi (a more frequent use of an AVF) and possibly for an improvement in morbidity and mortality, as suggested by previous studies on the benefits of nephrological monitoring before RRTi [4, 5].

Severe osteoporosis: Pandemic pick ups

Objective: During COVID-19 pandemic, the access to skeleton investigations for osteoporosis was in many cases postponed, thus consequences on fracture risk (FR) might be expected in terms of not continuing the antiosteoporotic medication or not initiating it if needed. Reduced physical activity might reduce the risk of fall, on one hand, but associated sarcopenia and inhibition of bone formation due to lack of physical exercise increase the FR, on the other hand (1-5). This is a case report of a female with severe osteoporosis who delayed the presentation for diagnostic during first 15 months of pandemic. Case report: This is a 73-year-old female, known with a history of osteoporosis since 2005. She also associates FR: chronic therapy with different SSRIs for depression, multinodular goiter-related hyperthyroidism (which was treated with radioiodine therapy). She has chronic therapy for arteria hypertension, hyperlipemia and hiatal hernia. At diagnostic, after initial lumbar T-score=-3.5 SD, she refused therapy until 2015 (when T-score decreased to -4 SD), thus she began therapy with intravenous ibandronate until 2017 when she experienced a vertebral fracture and daily 20 μg of teriparatide was initiated, starting from a DXA-BMD of 0.783 g/cm2, T-score of 3.1 SD. After 8 months, the treatment was stopped because of her lack of compliance, so she continued with annual zolendronic acid 5 mg until of T-score of -2.6 SD, BMD=0.856 g/cm2. In March 2020, when lockdown pandemic were initiated, she had to come to reassessment, but delayed it, and refused medication based on telemedicine recommendations, except for daily 1000 UI vitamin D. 14 months later, central DXA showed lumbar L1-3 BMD of 0.824 g/cm2, T-score of -2.9 SD, Z-score of -0.7 SD, hip BMD of 0.682 g/cm2, T-score of -2.6 SD, Z-score of -0.4 SD;25-hydroxyvitamin D of 29 ng/mL, PTH of 55 pg/mL, suppressed CrossLaps of 0.287 ng/mL (normal: 0.33-0.782 ng/mL), osteocalcin of 17 ng/mL (normal: 15-46 ng/ mL), P1NP of 27 pg/mL (normal: 15-45 pg/mL);an additional T4 thoracic fracture. Zolendronic acid was further recommended. Conclusion: During pandemic lockdown, the usual serial assays and decision of therapy were less adequate based on telemedicine.

Zolendronic acid after teriparatide: Pandemic observations

Objective: Teriparatide for sever osteoporosis is followed by antiresorptive drugs, and one option in patients with gastric intolerance is zolendronic acid or denosumab (1-5). During pandemic lockdown, the access to bone assessment was limited (1-5). Type 1 diabetic patients are particularly at risk for bone loss, but also for COVID-19 infection, thus the importance of respecting the pandemic rules (1-5). We aim to introduce a female case diagnosed with severe menopausal osteoporosis that was followed during post-teriparatide sequence of medication, including during pandemic days. Case report: This is a type 1 diabetic female of 77 y who was first diagnosed with menopausal osteoporosis 8 y ago (lumbar T-score of-3.1 SD) and started medication with weekly alendronate in addition to vitamin D supplements. After 3 y, she suffered a single spontaneous vertebral fracture thus teriparatide was initiated for 2 y (with good tolerance): lumbar T-score went from -3.1 to -1.9 SD. In the meantime, due to bilateral coxarthrosis she needed bilateral hip replacement. Further on, she continued with biannually denosumab for 8 injections, reaching a lumbar BMD-DXA 0.942 g/cm2, T-score of -2 SD, Z-score of -0.8 SD so an intravenous perfusion with zolendronic acid 5 mg was administered plus vitamin D supplements. While she had no additional fracture and glycated haemoglobin A1c remained around 6.2-6.4%, one year later, the pandemic started, so only bone turnover markers (BTM) were assessed, not DXA: suppressed CrossLaps=0.22 ng/mL (normal: 0.33-0.782 ng/ mL), osteocalcin=11 ng/mL (normal: 15-46 ng/mL), P1NP=27 pg/mL (normal: 15-45 pg/mL). She continued with vitamin D, and 20 months after injection CrossLaps remained low (=22 ng/mL) with normal osteocalcin (=15 ng/mL), P1NP (=28 pg/mL) and stationary BMD. Conclusion: Zolendronic acid effect in osteoporotic patients is easy to access by blood assays if DXA is not available, while lack of BTM increase is suggestive for a good outcome.

Hypovitaminosisd on an adult female: From autoimmune conditions to pandemic days

Objective: COVID-19 pandemic was associated with increased risk of hypovitaminosis D due to lockdown regulations and limited outdoor activities, while young adult patients with autoimmune conditions may associated decreased values of 25-hydroxyvitamin D due to copresence of celiac disease, glucocorticoid exposure, malabsorption, overtreatment of autoimmune hypothyroidism, etc. (1-5).We aim to introduce a female case known with autoimmune conditions who was admitted for vitaminD deficiency related symptoms during pandemic. Case report: A 41-year-old, nonsmoker female is admitted for nonspecific muscle cramps, and joints pain, asthenia which is persistent for the last several months in addition to chronic low back pain (which required chronic use of nonsteroid anti-inflammatory medication). Her personal medical background reveals a diagnosis of HLA-B27-positive ankylosing spondylitis that was established seven years before current admission. She is also known with autoimmune thyroiditis with negative antibodies, a diagnostic that was based on suggestive ultrasound features with highly hypoechoic pattern of relative small thyroid gland (and normal thyroid function). She is also confirmed with thrombophilia. She has a negative personal history of confirmed COVID-19 infection and she followed the lockdown restrictions for several weeks. The family medical history is irrelevant. On admission, clinical examination of the thyroid is within normal limits on amenstruated normal weighted female. Biochemistry data points out normal total calcium of 9.45 mg/dL (normal: 8.4-10.3 mg/dL). Endocrine panel shows TSH=1.28 μUI/mL (normal: 0.5-4.5 μUI/mL), free levothyroxine=11.65 pmol/L (normal: 9-19 pmol/L), anti-thyroperoxidase antibodies=10.88 UI/mL (normal: 0-35), anti-thyroglobulin antibodies=10 UI/mL (normal: 0-115 UI/mL). 25-hydroxyvitamin D=10 ng/mL (normal >30 ng/mL) with increased PTH levels and negative antibodies for celiac disease. Supplementation with daily 2000 UI of vitamin D for 12 weeks followed by daily 1000 UI was recommended. Conclusion: The association thrombophilia-hypovitaminosis D has been reported in some patients, but it is rather incidental. Chronic use of antiinflammatory medication may cause malabsorption, and also the potential of a second autoimmune disease at intestinal level may cause this deficiency, but the current pandemic reality has become a new cause of it.