Initiation Of Replacement Therapy Research Articles

Acute Cognitive Dysfunction in a Patient With Traumatic Brain Injury: A Clinical Vignette.

Acute Cognitive Dysfunction in a Patient With Traumatic Brain Injury: A Clinical Vignette.

Understanding International Variations in Kidney Failure Incidence and Initiation of Replacement Therapy

Incidence of kidney replacement therapy (KRT) varies widely across countries. Its relations to individual characteristics, nephrology practices for slowing chronic kidney disease (CKD) progression, and KRT access remain unclear. We investigated intercountry differences in kidney failure (KF) rate, defined by a sustained estimated glomerular filtration rate (eGFR)<15 ml/min per 1.73 m2, and separately in KRT incidence, before and after adjusting for risk factors and blood pressure (BP) control or renin-angiotensin-aldosterone system inhibitor (RAASi) prescription practices in the CKD Outcomes and Practice Patterns Study (CKDopps) cohort study. Among 7381 patients with CKD stage 3 to 4 at enrollment, 1297 progressed to KF and 947 initiated KRT over a 3-year follow-up period. Compared to the United States, demographic-adjusted and eGFR-adjusted hazard ratios (HRs) (HRs, 95% confidence intervals [CI]) for a sustained low eGFR were 0.77 (95% CI, 0.57-1.02) in Brazil, 0.90 (95% CI, 0.75-1.08) in France, and 1.03 (95% CI, 0.86-1.03) in Germany. Further adjustment for comorbidities, albuminuria, systolic BP, and RAASi prescription did not substantially change these HRs. In contrast, compared with the United States, the fully-adjusted HR for KRT remained significantly lower in Brazil (0.55, 95% CI 0.39-0.79), higher in Germany (95% CI, 1.36, 1.09-1.69), and similar in France (95% CI, 1.07, 0.81-1.39). Individual risk factors for CKD progression in nephrology patients appeared to explain most intercountry variations in KF but not KRT incidence. This suggests a prominent role for differences in practices related to KRT initiation or access, but not those for slowing disease progression. This study also shows that using KRT as a KF surrogate may bias estimates of associations with CKD progression risk factors.

Proximal spinal muscular atrophy 5q in the Republic of North Ossetia – Alania: population-genetic features, diagnostic problems and treatment prospects

This study presents the structure and population data of spinal muscular atrophy 5q in the Republic of North Ossetia – Alania. The number of newborns for the period 2000–2020 was 195 954, and the prevalence of spinal muscular atrophy 5q among newborns was 1:24 494, or 4.08 per 100.000. That corresponds to data on other populations of the Russian Federation and the world. We also describe intermediate results of the clinical efficacy of treatment of three spinal muscular atrophy 5q patients. Gene replacement therapy was used in two cases and combined pathogenetic and gene replacement therapy was used in the third case. No clinically significant decrease in the CHOP INTEND score from the baseline level was found in any patient during follow‑up. Clinical improvement was noted both during treatment with nusinersen and after administration of onasemnogene abeparvovec. Described clinical cases demonstrate the importance of early diagnosis and initiation of antisense oligonucleotide and/or gene replacement therapy, which is possible only when spinal muscular atrophy 5q is included in the neonatal screening program.

MO226: Is Remission of Hematuria Associated with Kidney Outcome in Biopsy-Proven Primary IGA Nephropathy?

Abstract BACKGROUND AND AIMS Microscopic hematuria, associated with variable proteinuria, is the most common clinical feature of IgA nephropathy (IgAN). However, its role in the disease progression is still controversial. This study aims to assess whether remission of hematuria is associated with kidney outcome in adults with primary IgAN. METHOD This retrospective, longitudinal study enrolled 62 adults, out of 214 with biopsy-proven IgAN between 1 January 2008 and 31 December 2017 {age 41 [95% confidence interval (CI) 37–46] years, 73% males, eGFR 41.3 (95% CI 33.1–51) mL/min and proteinuria 1.1 (95% CI 0.9–1.6) g/g} who had at least three assessment visits 3 months apart until 31 May 2018. The median follow-up period was 68 (95% CI 58.6–77.3) months. Demographic (age, gender), comorbidities, clinical and laboratory data (proteinuria, hematuria and blood pressure) at the time of kidney biopsy and during the follow-up period were retrieved from medical records. Information about therapy was also recorded. The study endpoint was kidney death defined as doubling of serum creatinine or renal replacement therapy (RRT) initiation. Kidney survival was evaluated by Kaplan–Meier method and variables related to kidney outcome by multivariate Cox proportional hazard modeling. Remission of hematuria was defined as ≤ 5 red blood cells/high power field in at least two samples taken no less than 3 months apart. Subjects were grouped as remission of hematuria (n = 24) and persistent hematuria (n = 38). RESULTS There were no differences between the two groups regarding demographic characteristics, comorbidities, kidney function, proteinuria, hematuria or inflammation markers at time of kidney biopsy. During the follow-up period, remission of proteinuria (defined as a &amp;gt; 50% decrease in urinary protein-to-creatinine ratio from baseline) was found in more than half of the group with remission of hematuria but in less than a quarter of group with persistent hematuria (57.1% versus 24.2%; P = .02). However, systolic blood pressure was well controlled (&amp;lt;130 mmHg) in similar proportions (63.6 versus 57.9%, P = .7) and a comparable reduction in mean arterial blood pressure from the baseline was observed [ΔMAP −7.8 (95% confidence interval (CI) −14.1 to −0.45) versus −2.8 (95% CI −9.7–4.9) mmHg; P = .2] in both groups. A high proportion of patients were treated with renin–angiotensin inhibitors (71 versus 61%; P = .5) and almost a third received immunosuppressive therapy (38 versus 34%; P = .8), similarly in the two groups. During the follow-up, a lower proportion of patients with remission of hematuria reached the composite kidney endpoint (16.7 versus 42.1%, P = .03). In the univariate time-dependent analysis, the kidney survival was numerically better in patients with remission of hematuria [(71.4 (95% CI 64.5–78.2) versus 66.02 (95% CI 54.7–77.2) months; log rank P = .06; Fig. 1A]. However, in the multivariate time-dependent analysis, only the absence of proteinuria remission [OR 0.06 (95%CI 0.008–0.46), P = .007] and a lower baseline eGFR [OR 0.96 (95% CI 0.93–0.98), P = .007] were associated with a poor kidney outcome (chi-squared = 18.5, P &amp;lt; .001) (Fig. 1B). CONCLUSION In this cohort of young adults with biopsy-proven primary IgA nephropathy and moderate decline in kidney function, the remission of hematuria for at least 3 months was not associated with kidney outcome.

A randomized controlled trial to evaluate and assess the effect of comprehensive pre-end stage kidney disease education on home dialysis use in veterans, rationale and design

BackgroundInformed dialysis selection and greater home dialysis use are the two long-desired, underachieved targets of advanced chronic kidney disease (CKD) care in the US healthcare system. Observational institutional studies have shown that comprehensive pre-kidney failure, conventionally referred to as end stage kidney disease education (CPE) can improve both these outcomes. However, lack of validated protocols, well-controlled studies, and systemic models have limited wide-spread adoption of CPE in the US. We hypothesized that a universal CPE and patient-centered initiation of kidney replacement therapy can improve multiple clinical, patient-centered and health service outcomes in advanced CKD and kidney failure requiring dialysis therapy.MethodsTrial to Evaluate and Assess the effects of CPE on Home dialysis in Veterans (TEACH-VET) is a multi-method randomized controlled trial aimed to evaluate the effects of a system-based approach for providing CPE to all Veterans with advanced CKD across a regional healthcare System. The study will randomize 544 Veterans with non-dialysis stage 4 and 5 CKD in a 1:1 allocation stratified by their annual family income and the stage of CKD to an intervention (CPE) arm or control arm. Intervention arm will receive a two-phase CPE in an intent-to-teach manner. Control arm will receive usual clinical care supplemented by resources for the freely-available kidney disease information. Participants will be followed after intervention/control for the duration of the study or until 90-days post-kidney failure, whichever occurs earlier.ResultsThe primary outcome will assess the proportion of Veterans using home dialysis at 90-days post-kidney failure, and secondary outcomes will include post-intervention/control CKD knowledge, confidence in dialysis decision and home dialysis selection. Qualitative arm of the study will use semi-structured interviews to in-depth assess Veterans’ satisfaction with the intervention, preference for delivery, and barriers and facilitators to home dialysis selection and use. Several post-kidney failure clinical, patient-centered and health services outcomes will be assessed 90-days post-kidney failure as additional secondary outcomes.ConclusionThe results will provide evidence regarding the need and efficacy of a system-based, patient-centered approach towards universal CPE for all patients with advanced CKD. If successful, this may provide a blueprint for developing such programs across the similar healthcare infrastructures throughout the country.Trial registrationNCT04064086.

Defining the role of Lyso-Gb1 as a biomarker over 12 months after first initiation of enzyme replacement therapy in patients with Gaucher disease in LYSO-PROVE study

Defining the role of Lyso-Gb1 as a biomarker over 12 months after first initiation of enzyme replacement therapy in patients with Gaucher disease in LYSO-PROVE study

A Hunter syndrome sibling pair: Differential effects of age at initiation of enzyme replacement therapy on growth, orthopedic disease, and daily living skills

A Hunter syndrome sibling pair: Differential effects of age at initiation of enzyme replacement therapy on growth, orthopedic disease, and daily living skills

Chronic kidney disease and cognitive impairment.

Chronic kidney disease (CKD) affects 25% of people over the age of 70. Neurocognitive disorders (NCDs) are frequent in patients with CKD and affect 30% to 60% of patients treated by haemodialysis. The link between CKD and NCD is explained by common risk factors, such as hypertension and diabetes, but also by CKD-specific risk factors through vascular, degenerative, and toxic mechanisms. In patients with non-dialysed CKD, albuminuria is more strongly linked to the occurrence of NCD than glomerular filtration rate. Vascular dementia is the main cause of NCDs in patients with CKD, but the incidence of Alzheimer's disease has also been found to be higher in patients with end-stage renal disease (ESRD) than in the general population. Executive functions, orientation and attention are the most frequently affected cognitive domains in patients with CKD. The occurrence of NCDs in older patients with CKD could be prevented by controlling blood pressure or by using anticoagulant drugs in the case of atrial fibrillation, which is particularly frequent in patients with CKD, in order to prevent cerebrovascular lesions. Nephrological care could also influence the occurrence of neurological complications. Anticholinesterase drugs and memantine should be used with caution in patients with CKD, as most of these drugs accumulate due to a low glomerular filtration rate. Due to the poor prognosis of patients with NCD and ESRD treated by dialysis or kidney transplantation, a cognitive assessment should be proposed in older patients with severe CKD in order to discuss the initiation and type of renal replacement therapy with both patients and caregivers.

Current aspects of heart-kidney interactions : Summary of important clinical studies from 2020

Chronisch nierenkranke Patienten weisen eine erhöhte kardiovaskuläre Morbidität und Sterblichkeit auf. Im letzten Jahr sind einige wichtige Studien zur Herz-Nieren-Interaktion veröffentlicht worden, die im Folgenden zusammengefasst und diskutiert werden. In der DAPA-CKD-Studie sowie in der SCORED-Studie konnten 2 unterschiedliche SGLT2(„sodium-glucose linked transporter 2“)-Inhibitoren (Dapagliflozin und Sotagliflozin) die Prognose von chronisch nierenkranken Patienten mit und ohne Diabetes nachweislich verbessern. Auch die Ergebnisse der randomisierten Studie zum neuen Mineralokortikoidrezeptorantagonisten Finerenon – FIDELIO-DKD – liefern einen vielversprechenden neuen Therapieansatz für Patienten mit diabetischer Nephropathie. Die veröffentlichten Daten der ISCHEMIA-CKD-Studie bei Patienten mit koronarer Herzkrankheit und Untersuchungen zum Einfluss einer TAVI („transcatheter aortic valve implantation“) auf die Nierenfunktion sowie eine weitere Studie zum akuten Nierenversagen nach MitraClip®-Implantation (Abbott, Chicago, IL, USA) geben wichtige Hinweise zu zukünftigen Handlungsempfehlungen. Der optimale Zeitpunkt der Einleitung einer Nierenersatztherapie bei Patienten mit akuter Nierenschädigung in der Intensivmedizin wurde in 2 randomisierten Studien untersucht, die entsprechend diskutiert werden.

Correlation of GAA Genotype and Acid-α-Glucosidase Enzyme Activity in Hungarian Patients with Pompe Disease.

Pompe disease is caused by the accumulation of glycogen in the lysosomes due to a deficiency of the lysosomal acid-α-glucosidase (GAA) enzyme. Depending on residual enzyme activity, the disease manifests two distinct phenotypes. In this study, we assess an enzymatic and genetic analysis of Hungarian patients with Pompe disease. Twenty-four patients diagnosed with Pompe disease were included. Enzyme activity of acid-α-glucosidase was measured by mass spectrometry. Sanger sequencing and an MLPA of the GAA gene were performed in all patients. Twenty (83.33%) patients were classified as having late-onset Pompe disease and four (16.66%) had infantile-onset Pompe disease. Fifteen different pathogenic GAA variants were detected. The most common finding was the c.-32-13 T > G splice site alteration. Comparing the α-glucosidase enzyme activity of homozygous cases to the compound heterozygous cases of the c.-32-13 T > G disease-causing variant, the mean GAA activity in homozygous cases was significantly higher. The lowest enzyme activity was found in cases where the c.-32-13 T > G variant was not present. The localization of the identified sequence variations in regions encoding the crucial protein domains of GAA correlates with severe effects on enzyme activity. A better understanding of the impact of pathogenic gene variations may help earlier initiation of enzyme replacement therapy (ERT) if subtle symptoms occur. Further information on the effect of GAA gene variation on the efficacy of treatment and the extent of immune response to ERT would be of importance for optimal disease management and designing effective treatment plans.

MO293NEUTROPHIL-TO-LYMPHOCYTE RATIO AND OUTCOME IN CRESCENTIC GLOMERULONEPHRITIS

Abstract Background and Aims Crescent formation is a nonspecific response to severe injury to the glomerular capillary wall, which may be seen with any form of inflammatory glomerulopathy. Despite improved therapeutic interventions, patients with crescentic glomerulonephritis (CGN) still have a severe kidney prognosis and high mortality. Since neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker linked to worse outcomes in patients with malignancies, chronic kidney disease, myocardial infarction, and other clinical settings, we aimed to assess if NLR can predict kidney outcome and mortality in subjects with CGN. Method Eighty-four adults with biopsy-proven CGN between 1st Jan. 2008 and 31st Dec. 2017 [age 56 (95%CI 53 to 59) years, 50% males, eGFR 9.3 (95%CI 7.8-12.7) mL/min] were retrospectively enrolled in this single-centre study. Subjects were followed for a median of 31 (95%CI 6 to 56) months, until 31st May 2018. Seven subjects with inadequate biopsy sample and insufficient data were excluded. Demographic (age, gender), clinical and laboratory data at the time of biopsy were obtained from medical records. Kaplan-Meier method was used to evaluate kidney and patient survival. Variables related to kidney outcome were evaluated in a multivariate Cox proportional hazard (CPH) model. According to median NLR value (4.3, 95%CI 3.5 to 5.2) subjects were clustered in low NLR group (≤4.3; n=38 pts.) and high NLR group (&amp;gt;4.3; n=38 pts.). The primary endpoints were time to renal replacement therapy (RRT) initiation and all-cause mortality. Results The most common CGN subtype was pauci-immune GN (76.3%; i.e. myeloperoxidase-ANCA vasculitis - 48.7%, PR3-ANCA vasculitis - 15.8% and ANCA-negative vasculitis - 11.8%) followed by. anti-GBM antibody and immune complex related GN, with similar frequencies (11.8% each). According to kidney biopsy (KB) findings, half of the subjects had fibro-cellular crescents (55.3%), while cellular and fibrous crescents were found in 35.5% and 9.2%, respectively. Almost all subjects received corticosteroids (97.4%) and 82.9% received cyclophosphamide. Baseline eGFR was lower in the high-NLR group (8.5 vs. 11.6 mL/min, p=0.04), but no other differences in laboratory findings at baseline between the two groups were found. In bivariate analysis, NLR was negatively associated with serum albumin (rs=-0.26, p=0.02). NLR was not associated with other inflammation markers, Charlson comorbidity score, nor with the type of crescents at KB. During the follow-up period 53.9% started RRT and 19.7% died. There were no differences regarding mortality between the two groups. The mean kidney survival time was 47.6 (95%CI 33.5, 61.7) months. Kidney survival at 12, 24, 48 and 60 months were 44, 41, 38, and 33% respectively. In univariate time-dependent analysis (Figure) patients with low-NLR (68.95%CI 48 to 88 months) had better kidney survival than those with high-NLR (25, 95%CI 13 to 38 months; log rank p=0.004). Moreover, the kidney survival advantage remained (OR 1.06, 95%CI 1.002 to 1.16) after adjusting for eGFR, proteinuria, C reactive protein, immunosuppressive treatment and CGN etiology. Lower eGFR-ul was also associated with poor kidney survival (OR 0.96, 95%CI 0.88 to 0.97). Conclusion In adults with biopsy-proven crescentic glomerulonephritis and advanced kidney function decline, a higher neutrophil-to-lymphocyte ratio seems to predict worse kidney survival, but not the risk of mortality.

547 Face Escharotomy in an Acute Deep Facial Burn

Abstract Introduction Escharotomy is the relaxation of the eschar through longitudinal or horizontal incisions in order to protect the region’s deep perfusion. The pressure that it will create in the peripheral areas such as hard eschar limb, trunk, and neck causes the circulatory disorder in the limb and the risk of limb loss, inadequate thoracic expansion in the thorax and vital perfusion and oxygenation problems in the neck. It is one of the most basic rules of burn surgery to perform the determined escharotomy incisions very quickly and without hesitation to prevent complications. In this report, a case of facial subunit principles based escharotomy is presented. Methods 42-year-old man felt into hot sand while working in an iron and steel factory. Patient was transferred to our burn unit for corresponding 35% of the total body surface burns on the face, neck and upper extremities. The patient was consulted to plastic surgery after the initiation of fluid replacement therapy, insertion of a chest tube for hemothorax, and tracheostomy. The patient had massive edema in the face and neck (Figure 1). There was no capillary fill in the facial skin. Doppler ultrasound examination showed bilateral weak facial artery, temporal superficial artery, supraorbital and trochlear artery flow. Results A decision was made to perform escharotomy to relieve arterial traces at 10th hour of the injury. Bilateral nasolabial, infraorbital rim, superior glabellar, temporal incisions were performed from eschar to subcutaneous fat layer in accordance with aesthetic subunits (Figure 2). Relief of the base perfusion during escharotomy was observed and bleeding was observed at the base of the incision. Doppler examination was repeated after escharotomy. The facial edema rapidly regressed. Deepitelization and reepithelization was observed in the areas with hair roots within 10 days and the patient was operated on the 15th day of hospitalization for debridement and skin grafting. Eschars were debrided and covered with split thickness skin grafts according to aesthetic subunit principles. Post-operative image of the patient seen (Figure 3). Conclusions Face is not an area in which eschar formation commonly seen because of its robust vascular supply and protection reflex of the patients. Although descriptive drawings and guides for facial escharotomy has not been published yet, relaxation of axial arteries in terms of compression due to eschar formation may be needed. In this report, a case of facial subunit principles based escharotomy is presented and acceptable results were achieved.

How to use dialysis wisely in cancer patients?

Both acute kidney injury (AKI) and chronic kidney disease (CKD) are common in cancer patients and are associated with inferior outcome, higher mortality rates, longer hospital stays and higher costs. In the aging population, the prevalence of both cancer and end-stage renal disease increase and practitioners are faced with difficult decisions regarding initiation of anticancer therapy and renal replacement therapy (RRT). Recent studies have shown no survival benefit of RRT ⩾80 years or even ⩾70 years in combination with severe comorbidities. However cancer itself does not seem to be a determining factor for short-term survival outcome and should not be used as argument alone to withhold RRT. Several prognostic tools can be implemented to identify elderly patients at high risk of functional decline and mortality after initiation of RRT. Advanced care planning focusses on timely discussions between patients, family members and practitioners about the patient’s desires and treatment goals which can help them avoid decisional conflict at the end-of-life and improve the quality of life.

Cumulative iodinated contrast exposure for computed tomography during acute kidney injury and major adverse kidney events.

To determine if contrast-enhanced CT imaging performed in patients during their episode of AKI contributes to major adverse kidney events (MAKE). A propensity score-matched analysis of 1127 patients with AKI defined by KDIGO criteria was done. Their mean age was 63 ± 16years with 56% males. A total of 419 cases exposed to CT contrast peri-AKI were matched with 798 non-exposed controls for 14 covariates including comorbidities, acute illnesses, and initial AKI severity; outcomes including MAKE and renal recovery in hospital were compared using bivariate analysis and logistic regression. MAKE was a composite of mortality, renal replacement therapy, and doubling of serum creatinine on discharge over baseline; renal recovery was classified as early versus late based on a 7-day timeline from AKI onset to nadir creatinine or cessation of renal replacement therapyin survivors. Sixty-two patients received cumulatively > 100mL of CT contrast, 143 patients had > 50-100mL, and 214 patients had 50mL or less; MAKE occurred in 34%, 17%, and 21%, respectively, as compared with 20% in non-exposed controls (p = 0.008 for patients with > 100mL contrast versus none). More contrast-exposed patients experienced late renal recovery (27% versus 20%) and longer hospital days (median 10 versus 8) than non-exposed patients (all p < 0.01). On multivariate analysis, cumulative CT contrast > 100mL was independently associated with MAKE (odds ratio 2.39 versus non-contrast, adjusted for all confounders, p = 0.005); cumulative CT contrast under 100mL was not associated with MAKE. High cumulative volume of CT contrast administered to patients with AKI is associated with worse short-term renal outcomes and delayed renal recovery. • Cumulative intravenous iodinated contrast for CT imaging of more than 100mL, during an episode of acute kidney injury, was independently associated with worse renal outcomes and less renal recovery. • These adverse outcomes including renal replacement therapy were not more frequent in similar patients who received cumulatively 100mL or less of CT contrast, compared with non-exposed patients. • More patients with CT contrast exposure during acute kidney injury experienced delayed renal recovery.

P0279DIABETIC KIDNEY DISEASE VERSUS CHRONIC KIDNEY DISEASE IN ADULTS WITHOUT DIABETES MELLITUS: A RENAL SURVIVAL ANALYSIS

Abstract Background and Aims Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease, but the decline in kidney function varies considerably between chronic kidney diseases (CKD), and determinants of renal function loss, early in the course of the disease, are still a matter of debate. Method We retrospectively examined the renal outcome at 31 July 2017 of 309 CKD patients (age 59.1 (50.1-68.6) years; 60% male; eGFR 32.7 (21.7-44.8) mL/min) admitted in our hospital during January 2007-December 2012 with a median follow up time of 7.2 (95%CI, 6.8-7.6) years. Only patients who had at least 3 admissions and who were alive during the study period were included. CKD was defined as the presence of an eGFR &amp;lt;60ml/min/1.73m2 or the presence of albuminuria &amp;gt;30mg/g creatinine for more than 3 months. The primary endpoint was renal survival defined as renal replacement therapy (RRT) initiation. Factors affecting renal survival were evaluated in a Cox proportional hazard model. Results DKD (24%), glomerular (GN, 24%), tubulo-interstitial (TIN, 27%) and vascular nephropathies (VN, 25%) were the causes of CKD. Patients with DKD (66.8 (56.5-72.2) years) and VN (68.5 (59.7-76.2) years) were older than those with GN (50.3 (37.4-59.0) years) and TIN (55.6 (45.8-61.8) years). Moreover, the highest cardiovascular comorbidity score was found in patients with VN and DKD (p&amp;lt;0.001). Median eGFR decline was -1.23 ( -3.39 – 0.35) mL/min/year; 29% of the patients had CKD progression of &amp;gt;3mL/min/year and 14% had rapid progression (&amp;gt;5mL/min/year). Patients with GN had the lowest eGFR (26.8 (19.1-38.9) versus DKD 36.2 (23.4-47.7), VN 34.9 (22.4-51.0), TIN 32.4 (21.8-44.8) mL/min, p&amp;lt;0.001), the fastest eGFR decline (-3.1 versus DKD -1.9, VN -1, TIN -1,2 mL/min/year, p 0.5) and the highest proteinuria (2.7 versus DKD 1.4, VN 0.4, TIN 0.6 g/24h, p&amp;lt;0.001). During follow up, 29% of the studied patients started RRT; mean renal survival time for the entire cohort was 7.4 (95%CI, 7.0-7.8) years. CKD cause (versus DKD p=0.04, Figure 1), lower eGFR (HR 0.89 (95%CI, 0.85-0.93)), elevated albuminuria (HR 1.4 (95%CI, 1.2-1.7)), higher total serum cholesterol (HR 1.00 (95%CI, 1.00-1.01)) and elevated mean arterial blood pressure (HR 1.03 (95%CI, 1.00-1.06)) were associated with RRT initiation in the Cox regression model. Conclusion Patients with DKD and VN had similar poorer renal survival as compared with GN and TIN. Earlier referral to the diabetic renal clinic and intensive management of the modifiable risk factors (albuminuria, hypercholesterolemia, hypertention) are necessary to retard progression of CKD and, subsequently, prolong renal survival.

P1548THE VALUE OF BEING A NETWORK: CLINICAL GOVERNANCE AND DIALYSIS CLINIC PERFORMANCE MANAGEMENT IS ASSOCIATED WITH IMPROVED PATIENTS SURVIVAL

Abstract Introduction. In order to help facilitate the uptake of best clinical practices, improve outcomes, enhance efficiency and reduce costs, few healthcare organizations have introduced Continuous Quality Improvement (CQI) programs. Since September 2014, dialysis centers belonging to the EMEA Fresenius Medical Care (FME) network have introduced a CQI policy called Medical Peer Review (MPR) based on key performance indicators (KPI) related to patient’s clinical status. We exploit the quasi-experimental setting generated by the introduction of FMC CQI policy, to evaluate the association between improvement in intermediate outcomes (key performance indicators) and prolonged survival among dialysis patients registered in the EMEA FME network. Methods. We conducted a historical cohort study. We included adult patients on chronic dialysis with less than 90 days between renal replacement therapy (RRT) initiation date and first treatment date in FME clinics. We compared KPI target achievement (P-BSC score) and 2-year mortality for patients enrolled prior to MPR-CQI policy onset (Cohort A) and a cohort of patients enrolled after MPR-CQI policy onset (Cohort B). Structural Equation model was adopted to estimate the association of MPR-CQI policy on patients’ survival through changes in intermediate outcomes (P-BSC score). Results. The Cohort A and Cohort B consisted of 2397 and 1873 patients, respectively. We observed no difference across groups concerning the distribution of age (63.1 vs 62.8 years), gender (59% vs 60% males) and body mass index (27.6 vs 26.4 kg/m2); Cohort A showed lower Charlson’s comorbidity index (3.3±1.5 vs 3.8±1.9, p&amp;lt;0.01) and higher dialysis vintage (32.9±27.0 vs 21.3±22.2 days, p-value&amp;lt;0.01) compared to Cohort B. P-BSC scores over the 6-month ascertainment period was 5.25±1.47 in the pre CQI-MPR policy cohort, while it was significantly higher (6.67±1.63) in the post CQI-MPR policy cohort. Mediation analysis demonstrated a strong indirect effect of CQI-MPR implementation on mortality trough improvement of P-BSC rating score occurring in the post-implementation era (OR=0.70, p&amp;lt;0.001) Conclusion. We showed that, after discounting for potential unmodifiable confounding factors and potential unmeasured selection/chronological bias, improvement of intermediate outcomes and performance indicators occurred after MPR-CQI policy implementation, was associated to a strong improvement in survival. Figure:

Infantile Hypophosphatasia: Clinical Case

Background . Hypophosphatasia is rare hereditary disease caused by deficiency of the tissue-nonspecific alkaline phosphatase isozyme. It manifests with bone and teeth mineralisation defects, electrolyte imbalance, respiratory disorders, convulsive syndrome, physical developmental delay, nephrocalcinosis. The rarity of this disease, clinical polymorphism, non-specificity of complains and signs are the major reasons of hypophosphatasia late diagnosis. The enzyme replacement therapy with recombinant alkaline phosphatase (asfotase alfa) can be used for treatment of severe forms of disease. Clinical Case Description . The girl (1 y 4 m) was routinely admitted with complains of physical developmental delay and psychomotor retardation, deformation of lower limbs, chest, gait abnormality, teeth loss and with diagnosis «protein-calorie malnutrition». Rickets-like changes in skeleton, myopathic syndrome, early normal teeth loss, hepatomegaly were revealed. Reduced activity of alkaline phosphatase in blood serum (33 u/l; reference range 156–369 u/l) was revealed. The infantile hypophosphatasia has been diagnosed. Due to molecular genetic testing of ALPL gene we revealed pathogenic variants c.526G>A (p.Ala176Thr) and c.1375G>A (p.Val459Met) in compound heterozygous state. The asphotase alpha therapy was initiated at the age of 1 y 10 m, the dose was 2 mg/kg subcutaneously 3 times a week. The results of 6 months of the therapy are the following: significant increase in the activity of alkaline phosphatase (maximum 4400 u/l), body weight (+ 2 kg), growth (+ 6 cm), reduction of bone deformation, normalisation of muscle tone and gait, exercise tolerance. The patient tolerated the drug administration well. Rarely there were hyperemia zones up to 4 cm in diameter with moderate induration at the injection site but they spontaneous disappeared in 2–3 days though. Conclusion. Patients with rickets-like diseases and low alkaline phosphatase activity requires performing of molecular genetic testing to confirm hypophosphatasia. Timely diagnosis and early initiation of enzyme replacement therapy can significantly improve the quality of life of children with hypophosphatasia.

Manufacturing of plasma-derived C1-inhibitor concentrate for treatment of patients with hereditary angioedema.

Background: Replacement therapy with plasma-derived C1-inhibitor (C1-INH) has been used for decades to treat patients with hereditary angioedema (HAE) with C1-INH deficiency. Objective: This article reviewed the rationale for using C1-INH replacement therapy in patients with HAE and the process of manufacturing plasma-derived C1-INH. Methods: The manufacture of C1-INH is an involved and carefully monitored process that includes screening and selection of prospective donors, the collection of source plasma, and purification with dedicated pathogen reduction steps. Donor eligibility is determined by restrictive criteria established and monitored by regulatory agencies as well as voluntary standards implemented by plasma collection centers that exceed government regulations. Individual and pooled donations are tested for transfusion-transmissible infections, including hepatitis B virus, hepatitis C virus, human immunodeficiency virus, parvovirus B19, and hepatitis A virus, by using enzyme-linked immunosorbent assays or nucleic acid amplification technologies. Frozen plasma that is cleared for manufacturing undergoes controlled thawing and centrifugation, and the resulting supernatant (i.e., cryoprecipitate-depleted plasma) is used to manufacture several plasma-derived therapies, including C1-INH. In addition to chromatography steps, the manufacturing process consists of dedicated and effective pathogen reduction steps, including pasteurization, hydrophobic interaction chromatography or polyethylene glycol precipitation, and virus filtration. Manufacturers continuously monitor the safety profile of C1-INH products by robust pharmacovigilance processes that enable systematic collection and evaluation of all suspected adverse drug reaction reports as well as evaluation of safety information from all other sources. Results and Conclusion: These procedures used in donor screening, donation and manufacturing pool testing, manufacturing, and pharmacovigilance ensure that plasma-derived C1-INH products have the safety, quality, identity, potency, and purity that is necessary to provide the intended therapeutic effect.

Case Report: Pancytopenia as an indicator for lysosomal storage disease (Gaucher's Disease)

Introduction: Lysosomal storage disorders are a rare group of diseases with genetic origin in which Gaucher Disease (GD) stands out as the most frequent. GD type 1 is the most common form of this condition, and patients with this pathology present with unexplained cytopenias, in addition to hepatosplenomegaly, bone involvement, and in other cases neurological disorders. A case of a patient is presented, whose results showed thrombocytopenia and leukopenia in addition to hepatosplenomegaly. In Latin America, there are very few reported cases of this clinical entity, and information on this disease is very limited. Case: We present a case of a patient diagnosed with GD, who presented with thrombocytopenia and leukopenia in addition to hepatosplenomegaly, with the aim of emphasizing the importance of early recognition of this pathology, especially in patients with unexplained cytopenia’s or hepatosplenomegaly’s. In suspicion of GD, enzymatic quantification of β-glucocerebrosidase was performed, showing its deficit in addition to alteration in the GBA gene. Unfortunately, enzymatic replacement could not be done because the Cerazyme (imiglucerase for injection) is not available in Ecuador. Nevertheless, the patient was treated with analgesic (1g of paracetamol generally three times a day) and vitamin supplements (Dayamineral). Currently the patient is waiting for transfer to a foreign institution; she continues with bicytopenia and hepatosplenomegaly, her conditions are expected to be remit once the enzymatic treatment has been administered. Conclusion: We believe that the timely recognition of this disease will allow the initiation of enzymatic replacement therapy in an effective manner, in order to reduce morbidity and improve the clinical aspects of the patient.

Clinicopathologic features and prognosis of patients with IgA nephropathy superimposed on transplant glomerulopathy

Objective: To observe the clinicopathologic features and prognostic of patients with IgA nephropathy (IgAN) superimposed on transplant glomerulopathy (TG+ IgAN). Methods: Electronic medical records of Jinling Hospital were searched for TG+ IgAN patients that was diagnosed during January 2004 to December 2016. Clinicopathologic features and prognoses information were retrieved and analyzed. The primary outcome was initiation of replacement therapy or an eGFR declined to<15 ml·min(-1)·(1.73m(2))(-1). Results: A total of 49 patients with pathologically confirmed TG+ IgAN were enrolled in this study. The median time from renal transplantation to allograft biopsy was 85 months. There were 131 patients with TG in the control group. There was no statistical difference in the age, gender, and immunosuppressive regimen during renal biopsy in the two groups. In TG+ IgAN patients, the median serum creatinine level was 175 μmol/L, the median urinary protein was 1.45 g/24 h, and 16.3% of the patients had nephrotic range proteinuria, the incidence of microscopic hematuria was 40.8%, and the average hemoglobin was 105 g/L. In terms of pathology, the degree of glomerular mesangial matrix hyperplasia in the TG+ IgAN group was significantly heavier compared with TG group (P=0.004), and the degree of hyaline degeneration of the small arteries was lighter (P=0.043). There was no significant difference in interstitial inflammation (i), tubulitis (t), glomerulitis (g), peritubular capillaritis (ptc) and intimal arteritis (v). Calculated by Kaplan-Meier method, the median survival time of 49 patients with TG+ IgAN was 36.9 months, and there was no difference in survival rate of allografts compared with TG group. Conclusions: Compared with TG patients without IgA, TG+ IgAN patients had higher incidence of microscopic hematuria, more severe glomerular mesangial matrix hyperplasia, and no significant differences in other clinicopathological features. The prognosis of TG+ IgAN patients was not significantly different from those without IgAN.