Mild Renal Failure Research Articles

Lymphocyte Levels and Morbidity and Mortality in Cardiovascular Surgery With Cardiopulmonary Bypass.

A year ago, in a sample of 113 patients, our research group found that a high number of lymphocytes in the immediate postoperative period was correlated to a poor prognosis in cardiovascular surgeries. This study is an expansion of the initial study in order to confirm this finding. We analyzed the data of 338 consecutive patients submitted to cardiovascular surgeries with cardiopulmonary bypass performed at Hospital Universitário Ciências Médicas (Belo Horizonte/Brazil) from 2015 to 2017. We analyzed 39 variables with the outcomes death, hospital stay, and intensive care unit stay. The value of lymphocytes in the immediate postoperative period > 2175.0/mm³ was an indicator of poor prognosis in this sample (P<0.001). The variables female sex, age, high level of European System for Cardiac Operative Risk Evaluation II, increased stay in the intensive care unit and in the ward, elevation of creatinine in the preoperative period and at intensive care unit discharge, elevation of the percentage of immediate postoperative period segmented neutrophils, high immediate postoperative period neutrophil/lymphocyte ratio, fasting hyperglycemia, preoperative critical condition, reintubation, mild or transient acute renal failure, surgical infection, cardiopulmonary bypass, and aortic cross-clamping and mechanical ventilation durations also had an impact on the mortality outcome. The value of lymphocytes in the immediate postoperative period > 2175.0/mm3 was an indicator of poor prognosis in cardiovascular surgery with cardiopulmonary bypass.

Real life experience on the use of Remdesivir in patients admitted to COVID-19 in two referral Italian hospital: a propensity score matched analysis

Remdesivir (RDV) was the first Food and Drug Administration (FDA)-approved medication for COVID-19, with discordant data on efficacy in reducing mortality risk and disease progression. In the context of a dynamic and rapidly changing pandemic landscape, the utilization of real-world evidence is of utmost importance. The objective of this study is to evaluate the impact of RDV on patients who have been admitted to two university referral hospitals in Italy due to COVID-19. All patients older than 18 years and hospitalized at two different universities (Bari and Palermo) were enrolled in this study. To minimize the effect of potential confounders, we used propensity score matching with one case (Remdesivir) and one control that never experienced this kind of intervention during hospitalization. Mortality was the primary outcome of our investigation, and it was recorded using death certificates and/or medical records. Severe COVID-19 was defined as admission to the intensive care unit or a qSOFAscore ≥ 2 or CURB65scores ≥ 3. After using propensity score matching, 365 patients taking Remdesivir and 365 controls were included. No significant differences emerged between the two groups in terms of mean age and percentage of females, while patients taking Remdesivir were less frequently active smokers (p < 0.0001). Moreover, the patients taking Remdesivir were less frequently vaccinated against COVID-19. All the other clinical, radiological, and pharmacological parameters were balanced between the two groups. The use of Remdesivir in our cohort was associated with a significantly lower risk of mortality during the follow-up period (HR 0.56; 95% CI 0.37–0.86; p = 0.007). Moreover, RDV was associated with a significantly lower incidence of non-invasive ventilation (OR 0.27; 95% CI 0.20–0.36). Furthermore, in the 365 patients taking Remdesivir, we observed two cases of mild renal failure requiring a reduction in the dosage of Remdesivir and two cases in which the physicians decided to interrupt Remdesivir for bradycardia and for QT elongation. Our study suggests that the use of Remdesivir in hospitalized COVID-19 patients is a safe therapy associated with improved clinical outcomes, including halving of mortality and with a reduction of around 75% of the risk of invasive ventilation. In a constantly changing COVID-19 scenario, ongoing research is necessary to tailor treatment decisions based on the latest scientific evidence and optimize patient outcomes.

Inhibition of the Progression of Chronic Kidney Disease With Hyperuricemia

The final product of the catabolism of purine compounds in humans is uric acid (UA), which is a weak organic acid, over 98% of which is ionized into monosodium urate. UA is excreted by the kidneys, approximately 80-99% is reabsorbed in the proximal tubules of the kidneys. About 20% of UA is excreted through the intestine, where it is destroyed by microflora to carbon dioxide and water. The reference value of UA in blood plasma is 6.5-7 mg/dl in men and 6–6.5 mg/dl in women. The content of UA in the range of 360-400 μmol/l or 6-6.8 mg / dl increases the risk of crystallization under physiological conditions, and regardless of gender. UA levels greater than 7.0 mg/dl are associated with an increased risk of developing gout or nephrolithiasis. Hyperuricemia may occur due to increased production and / or decreased renal excretion of UA. Hyperuricemia is high in the general population and is associated with the development and progression of chronic kidney disease (CKD). Currently, allopurinol and febuxostat are used to correct hyperuricemia. The use of allopurinol should begin with a low dose (50-100 mg/day) and gradually titrate until the target level of UA in the blood is reached or until it is reached to the maximum. If necessary, the dose of allopurinol is increased by 100 mg every 2–4 weeks until the target serum UA level is reached. According to EULAR's recommendations for the treatment of gout, if the target level of UA cannot be achieved with an adequate dose of allopurinol, it should be replaced with febuxostat or uricosuric or a combination of febucostat with uricosuric. Febuxostat is also indicated for allopurinol intolerance. Febuxostat in doses of 80 and 120 mg/day was more effective than allopurinol at a dose of 300 mg/day. With CKD with mild or moderate renal failure, as well as in the elderly, it is not necessary to adjust the dose of febuxostat. The likelihood of reaching the target level of UA in the blood with reduced kidney function is higher in febuxostat. If the patient does not have serious cardiovascular diseases, the patient can be transferred to febuxostat, starting with a dose of 40 mg/day, and gradually titrated, especially in the case of CKD.

Impact of mildly reduced kidney function on 5-year mortality in patients with STEMI treated with primary PCI

Abstract PURPOSE Previous research associated renal failure (RF), as documented by estimated glomerular filtration rate (eGFR) &amp;lt;60 ml/min/1.73m2, with increased mortality risk following acute myocardial infarction. Our aim was to assess the impact of baseline mild RF (eGFR 60-89 ml/min/1.73m2) on mortality during 5-year follow-up after ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). Methods The study included 8378 STEMI patients undergoing primary PCI in the period from 2009 until 2019 for whom baseline eGFR data were available, according to the Modification of Diet in Renal Disease (MDRD) study equation. Cox regression models were created to assess the effect of different stages of renal failure on 30-day and 5-year mortality. Follow-up data were available for 8202 patients at 30 days and 5650 patients at 5 years. Results Renal function was impaired in 49% of patients (eGFR &amp;lt;30 ml/min/1.73m2 in 2.5%, eGFR 30-59 ml/min/1.73m2 in 16.2% and eGFR 60-89 ml/min/1.73m2 in 30%). Patients with eGFR &amp;lt;90 ml/min/1.73m2 had higher mortality rates at 30 days (10.0% vs. 1.7%, p&amp;lt;0.001) and at 5 years (44.1% vs 13.5%, p&amp;lt;0.001). Mortality increase was synchronous with the degree of renal failure at both 30 days and 5 years (Figure, panel A and B, respectively). At 30-days, patients with mild RF had higher adjusted mortality compared to patients with eGFR&amp;gt;90 ml/min/1.73m2 (HR 1.6, CI95% 1.1-2.4, p 0.027). At 5 years, eGFR 60-89 ml/min/1.73m2 was also associated with the higher adjusted mortality (HR 1.4, CI95% 1.2-1.6, p&amp;lt;0,001). As expected, severe (eGFR &amp;lt;30 ml/min/1.73m2) and moderate (eGFR 30-59 ml/min/1.73m2) renal failure was associated with a higher risk of mortality (30 days: HR 4.4 and 2.6 respectively; 5 years: HR 3.7 and 2.2 respectively). Conclusions The risk of short- and long-term mortality after STEMI increases proportionally with the degree of baseline renal failure. Compared with patients with a normal renal function, even mild renal failure (eGFR 60-89 ml/min/1.73m2) is associated with higher mortality at both 30 days and 5 years.

Renal function in patients with rheumatoid arthritis in Rafsanjan city in 2021

Renal involvement is one of the extra-articular manifestations of rheumatoid arthritis (RA). The current study aims to investigate renal function and its associated factors in RA patients. This cross-sectional study included 443 RA patients who were referred to Rafsanjan's only rheumatology clinic in 2021. Disease Activity Score 28 (DAS28) index was used to determine disease activity. Blood levels of creatinine, C-Reactive Protein test (CRP), Erythrocyte Sedimentation Rate (ESR), and urine analysis were also determined. Renal failure was classified based on Estimated Glomerular Filtration Rate (eGFR). SPSS.20 one-way ANOVA, Kruskal-Wallis test, the Mann-Whitney U test, and Chi-square were used to analyze the data. Patiens' mean age was 53.99 ± 12.34, and 85.8% (380 people) of the participants were female. Ther were 147 (33.2%) patients without renal failure, 260 (58.7%) with mild renal failure, and 36 (8.1%) with moderate/severe failure. Men had a 3.059 higher risk of renal failure than women (P = 0.001). The probability of developing renal failure in patients increased by 1.047 times with each year of age (P &lt; 0.001). As a chronic disease, RA can directly or through the use of disease medications and other risk factors, adversely affect other organs of the body, including the kidney. The current study's findings revealed a high prevalence of mild renal failure in these patients.

#4215 MONOALLELIC IFT140-RELATED POLYCYSTIC KIDNEY DISEASE IN AN ITALIAN ADPKD COHORT

Abstract Background and Aims Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder characterized by progressive bilateral renal cysts development and extrarenal phenotype, i.e. liver and/or pancreatic cysts, intracranial aneurism, hernias, mitral valve prolapse and diverticulosis. More than 90% of patients harbour heterozygous pathogenic variant in PKD1 or PKD2 genes, rarely in other cystogenes (e.g. GANAB, DNAJB11, ALG8, ALG9). Recently Senum et al. demonstrated that monoallelic loss of function (LoF) IFT140 variants are an important cause of ADPKD-like disease distinguished by large renal cysts, few liver cysts and mostly mild renal failure. The aim of our study was to define prevalence and phenotype of IFT140-ADPKD in an Italian ADPKD cohort. Methods The study included ADPKD patients, evaluated in 2021 and 2022, at Outpatient Clinic of Genetic Kidney Diseases of Brescia, Italy, that underwent in-depth clinical, laboratory, and instrumental assessments. ADPKD was clinically diagnosed according to Pei modified criteria, in patients with age-specific ultrasound criteria and family history consistent with autosomal dominant inheritance. From January 2022, NGS genetic testing protocol for ADPKD has been updated with IFT140 gene, thus the ADPKD gene panel included: ALG8, ALG9, ANKS6, DNAJB11, GANAB, IFT140, LRP5, PARN, PKD1, PKD2, PRKCSH, SEC61A1, SEC63. The new protocol has been offered to patients evaluated since January 2022 and to all genetically unresolved patients evaluated in 2021. All patients performed also multiple ligation probe amplification (MPLA) analysis of PKD1 or PKD2. Results In 2021 and 2022 ADPKD genes testing has been performed in 129 patients. Pathogenic variants in PKD1 or PKD2 genes were detected in 110/129 patients (85%); among the negative cases (19/129, 15%), 3 patients (P1,P2,P3) resulted heterozygous carrier of LoF variants in IFT140 gene: p.Arg307*, p.Lys1275Argfs*23 and p.Arg834* respectively. Overall 2,3% of ADPKD patients harboured IFT140 pathogenic variant; considering unresolved cases only, the prevalence was 15.7% (3/19). Segregation analysis identified the LoF variant in 3 daughters of P1 and in a son of P2. The 3 probands were diagnosed with renal disease in adulthood from fourth to sixth decade. In P1 eGFR (CKD-EPI formula) slowly declined from 104 ml/min/1.73 at onset (43 year-old) to 74.6 ml/min/1.73 at age 55. In P2 eGFR at first evaluation was 38 ml/min/1.73 (68 year-old); at last follow-up 32.9 ml/min/1.73 (73 year-old). In P3 eGFR declined from 51.7 ml/min/1.73 (55 year-old) to 42 ml/min/1.73 at age 67. Renal imaging in P1 at and P2 disclosed increased total kidney volume (TKV 1042 and 5520 cc respectively), large cysts and absence of cystic liver disease. P3 had slightly increased kidneys (TKV 447cc) with large renal cysts and few liver cysts. Hypertension was present in 4 patients, all with adult-onset (46-60 years). Two patients had an early diagnosis of kidney stones (age 24 and 18). No macroscopic hematuria or cyst infections were reported. In accordance with an ADPKD-like disease form, P1 presented inguinal hernia. Imaging data are summarized in Figure 1. Conclusion In this Italian cohort, heterozygous LoF variants in IFT140 gene is confirmed to be the third most common genetic cause of ADPKD-spectrum disease, the prevalence being 2,3%. The major features are late onset hypertension, increased kidney volume due to large cysts and slow progressive renal failure. IFT140 gene must be included in diagnostic protocol of ADPKD patients to better define renal prognosis, therapy and familial screening.

#4154 CIRCULATING BETA-TRACE PROTEIN VERSUS CREATININE AS MARKERS OF EARLY KIDNEY (DYS)FUNCTION IN THE NX-INDUCED RAT MODEL OF CHRONIC KIDNEY DISEASE

Abstract Background and Aims Beta trace protein (BTP) is a low molecular weight protein that has been proposed as an earlier biomarker of decreased glomerular filtration rate (GFR) and renal damage, than the traditional biomarkers, particularly in the creatinine blind range. Early biomarkers of renal (dys)function are needed to allow, in due time, the detection and treatment, to prevent worsening of the disease. To the authors’ knowledge, neither urine nor serum BTP has been assessed in animals with kidney disease. In the present study, we aimed to concomitantly evaluate BTP and creatinine circulating levels, to compare their value as early biomarkers of renal dysfunction, by performing the studies in rat models of mild and moderate chronic renal failure (CRF) induced by nephrectomy. Method Male Wistar rats, 12 weeks old, were randomly divided in three groups: Sham (n = 8, subjected to surgical process without kidney mass reduction), Mild CRF (n = 8, subjected to 1/2 nephrectomy), and Moderate CRF (n = 7, subjected to 5/6 nephrectomy). After five weeks, rats were sacrificed, blood and kidneys were collected. We analysed the circulating levels of BTP and creatinine and studied the association of BTP concentration with the glomerular and tubulointerstitial lesions, and with the traditional biomarkers of renal (dys)function, eGFR and creatinine. Results The serum levels of BTP were correlated with serum levels of creatinine (r = 0.575, p = 0.004) and also with eGFR (r = -0.453, p = 0.030); additionally, we found positive correlations with the total score of mild and advanced tubular lesions (r = 0.610, p = 0.02 and r = 0.517, p = 0.011, respectively), observed in kidney sections. The circulating levels of BTP increased with disease severity; Mild CRF showed a higher value of BTP than Sham group, although without statistical significance that was reached in Moderate CRF group, as observed for serum creatinine. The combined use of BTP and creatinine did not improve the discriminatory power in early disease detection. Though, the combination showed stronger correlations with the total score of tubular lesions (r = 0.849, p &amp;lt; 0.001 for mild tubular lesions and r = 0.774, p &amp;lt; 0.01 for advanced tubular lesions). Conclusion In rat models of mild and moderate CRF induced by nephrectomy, serum BTP levels increased with kidney function worsening, and correlated with disease severity, assessed by GFR and the degree of histopathological alterations. However, the earlier diagnostic value of BTP does not outperform serum creatinine in this model.

P1328: SUCCESFUL TREATMENT OF GRAFT FAILURE IN AUTOLOGOUS STEM CELL TRANSPLANTATION WITH CYCLOSPORINE

Background: Graft failure is an unusual complication of autologous stem cell transplantation (ASCT). It is a life threatening complication where most patients (pts) die because of infections or bleeding. It is defined by absence of neutrophil recovery (>500 ANC) on day +28. It can be primary (there wasn´t a previous neutrophil recovery) or secondary (if there was). Ruling out infections, toxicity of conditioning or poor quality of cells infused, the main cause is still unknown. There is no much literature about GF in ASCT. Treatments proposed are cellular reinfusion or search of a donor for allogeneic stem cell transplantation with poor results. Aims: The aim of this study is to describe our experience in treating such a rare ASCT complication. Primary endpoint is the obtainment of neutrophils (>500) and the platelet engraftment (>20.000) with no transfusion-dependence. Methods: Between 2010 and 2021 a total of 706 pts underwent an ASCT in our institution. 5 pts presented a primary (n=4) or secondary (n=1) GF. We collect the data from these patients. Results: Our incidence of GF is 0.71%, making GF a rare complication of ASCT. 4 pts had a primary GF and 1 had a secondary GF. Peripheral blood was the source in the pts; who were mobilized with G-CSF without any complication. All the pts were infused with more than 2 x106 CD34+ cells /kg (median number of 2.7 (2.2 -3.4)) without any manipulation of the graft. The median viability was 96% (92-99.7). None of the pts had splenomegaly or bone marrow infiltration at the moment of ASCT. These 5 pts had different hematological diseases (3 Multiple Myeloma (MM), 1 composite lymphoma (CL) and 1 primary nervous system lymphoma (PCNSL)). The status of response at ASCT was 3 CR, 1 VGPR (1 MM) and 1 PR (PCNSL). The conditioning regimen used was BUMEL (2 MM), MEL200 (1 MM) BEAM (1 CL) and TT-BCNU (1 PCNSL). All the pts received G-CSF from day +5 after cell infusion. Bone marrow biopsy was made in 3 of these pts, with severe hypoplasia without fibrosis. After diagnosis of GF, in all the pts, the first line treatment was increased dose of G-CSF. 4 pts were also treated with corticoids without any response. 2 pts additionally received previously cryopreserved cells without response. We started empiric treatment with CsA at an initial dose of 1.5mg/kg twice daily in these pts and the median time to reach>500 ANC was 5 days (4-9). Three of these pts could stop CsA treatment after 30 days due to recovery of neutrophil and platelet count. Another one had to be under treatment 150 days. The last one is still on treatment (after 2 months). With a median follow up of 90 months (2-91) all the pts are alive and with a good neutrophil and platelet engraftment. In terms of security, 2 pts developed mild renal failure, managed by dose adjust. No other adverse events were seen in these pts. Summary/Conclusion: CsA is an immunosuppressive drug widely used in aplastic anemia and other bone marrow failure syndromes, due to suppression of haematopoiesis by autoreactive T- lymphocytes. This can also be the pathogenic mechanism of GF. We successfully used empirical CsA treatment in these pts. All the pts but one had an ANC>500 in the first week of treatment with CsA and were able to discontinue the drug soon. Severe infections due to neutropenia are the first causes of death in pts with GF so improvement of ANC decrease is the main goal in the treatment of GF. As CsA is a secure drug, we propose to urgently include this treatment as a curative option in the algorithm of GF management to be taking into account before the allogeneic stem cell trasplantation option.

Vascular embolization of radiopaque hydrogel microfiber using ultra-minimally invasive technique for stage-adjustable renal failure model

Animal pathology models play an important role in elucidating pathology, evaluating drug efficacy, and studying therapeutic. This paper presents the creation of rats’ renal failure model by embolizing the renal artery using radiopaque hydrogel microfibers. By using a dual coaxial laminar flow microfluidic device, barium alginate gel microfibers containing zirconia particles were fabricated. Since the zirconia particles are radiopaque, the microfiber can be delivered and embolized while confirming the position of the microfiber in real-time under X-ray imaging. The delivery of microfibers through a catheter into the renal artery of rats to create a renal failure model was tested. The radiopaque microfibers were visualized by X-ray imaging when delivered by a catheter. Furthermore, the microfibers remained stable for 2 weeks after delivery. In addition, by adjusting the number of microfibers, two different rat models with severe and mild renal failure conditions were created. The proposed delivery of radiopaque hydrogel microfibers to create an embolization model is expected to be an effective approach to control the degree of symptoms and elucidate the pathology.

Effectiveness and Safety of Low Dose of Tenofovir Disoproxil Fumarate in Malagasy Patients with Chronic Hepatitis B.

Background Accessibility of full dose daily of tenofovir disoproxil fumarate (TDF) is limited in Madagascar with an estimated cost well above the purchasing power of Malagasy population. Objective The study is aimed at evaluating the efficacy and safety of low-dose tenofovir for the treatment of chronic hepatitis B (CHB). Methods This prospective cohort study from January 2018 to December 2020 was conducted in the Department of Hepato-Gastroenterology, University Hospital Joseph Raseta Befelatanana, Antananarivo, Madagascar. The patients enrolled in the study received low dose of TDF 900 mg/week (300 mg daily, three days per week). Results A total of 45 patients (male/female: 31/14) were included. The mean age was 45.1 ± 11.5 years. Fifteen patients were nucleos(t)ide (NA)-naïve, and 30 patients had prior NA therapy (NA-experienced). Thirty patients were HBeAg positive. A complete virological response (CVR) was achieved in 36/45 patients (80%) at 3 months, 41/45 (91.1%) at 6 months, and 43/45 (95.6%) at 12 months. High viral load at baseline was negative predictive factor of CVR at 3 months (HR: 0.14; 95% CI: 0.022–0.92; p: 0.041). There was no significant difference in response between HBeAg-positive and HBeAg-negative patients, NA-naïve and NA-experienced patients, and cirrhotic and noncirrhotic patients. Low dose of tenofovir was well tolerated. Ten patients (22.22%) had mild side effects. Mild renal failure was observed in 3 patients (6.7%) during follow-up. Conclusion Low dose of tenofovir is effective, safe, and well tolerated in a Malagasy population sample. These results still require verification in a large population.

Frequency of renal tubular acidosis in children with down syndrome

Background: Down syndrome (DS) is associated with various congenital diseases and malformations, including those of the kidneys and urinary tract. It has been thought that renal tubular acidosis (RTA) is more frequent in this population. The objective of this study was to assess the frequency of RTA and, secondarily, of other renal and urological disorders in persons with DS. Method: An observational, ambispective, descriptive and cross-sectional study of patients diagnosed with RTA, or suspected kidney or urological disorders, was carried out from July 2016 to September 2017 at the Down syndrome clinic of the Mexican National Institute of Paediatrics. Urinalysis was performed, along with analyses of venous blood gas, sodium, potassium, chlorine, calcium, phosphorus, albumin and creatinine. Those with any abnormal values were referred to nephrology for diagnostic evaluation. Results: Of a total of 700 patients seen at the clinic, 47 met the selection criteria. Of these, 32 had no RTA or other renal or urological alterations. The remaining 15 continued to the second phase of the study, where 6 were diagnosed with nephropathy or uropathy (RTA, systemic arterial hypertension, monosymptomatic familial haematuria, mild renal failure secondary to reflux nephropathy, urinary tract infection or right ureteropelvic stenosis). Four had mild metabolic acidosis without meeting the criteria for diagnosis of RTA. Conclusion: RTA is not more common in children with Down syndrome. Nephropathies and uropathies should be investigated in the evaluation of DS patients.

699-P: Assessment and Management of Falling in Type 2 Diabetic Patients with Diabetic Kidney Disease

Background: Older type 2 diabetic patients are at an increased risk of falling. On the other hand, the risk of sarcopenia increases in patients with chronic renal disease. In the present study, we reported about the risk of falling in type 2 diabetic patients with diabetic kidney disease (DKD). Methods: Participants were 111 outpatients with type 2 diabetes at our hospital (66.1±8.8 years old). We measured one-leg standing (OLS) time with eyes open and analyzed the date according to renal function. Participants were defined as patients with a high risk of falling, if their OLS time was less than 20s. In order to examine the cause of short OLS time, we measured the ten times sit to stand test (TTSTS) and toe grip strength test (TGST). Furthermore, we measured hand grip strength, the timed up and go test (TUG), skeletal muscle mass (Inbody S10, Biospace, Tokyo, Japan), and evaluated diabetic peripheral neuropathy (DPN) by DPN Check (HDN-1000, Omron, Tokyo, Japan). At last, we planned original physical therapy for patients. Result: A total of 101 cases (60 males; 51 females) were included in this study. The prevalence of patients with a high risk of falling was 60.0%. In patients without renal failure (eGFR ≥ 60 ml/min/1.73 m2), with mild renal failure (30 ≤ eGFR &amp;lt; 60), and with sever renal failure (eGFR &amp;lt; 30), the prevalence of patients with a high risk of falling was 48.1%, 67.9%, and 81.8 % respectively. Patients with a short OLS time tended to perform the TTSTS more slowly than patients with a normal OLS time. Short OLS time is also associated with TGST. Patients with DPN did badly on the TGST. Based on this result, we provided patients with a physical therapy program and diet therapy. Conclusion: These findings showed that the OLS time was significantly shorter in type 2 diabetic patients, especially those with advanced DKD. Therefore, exercise therapy, diet therapy including a good quality protein intake and management of complication including diabetic DPN are important for type 2 diabetic patients with DKD. Disclosure S. Ikejima: None. T. Takahashi: None. S. Kondo: None. J. Umezu: None. M. Uema: None. A. Hirai: None.

Hyperthyroidism influences renal function.

While the effects of hypothyroidism on renal function have been studied extensively, there is less information concerning the effect of hyperthyroidism. We aimed to elucidate the effect of overt and subclinical hyperthyroidism, on estimated glomerular filtration rate (eGFR) with large number of patients treated for hyperthyroidism and after euthyroidism was achieved. A total of 433 consecutive overt and subclinical hyperthyroid patients were included in the study. We assessed serum fT3, fT4, TSH, BUN, creatinine, and eGFR measurements during both hyperthyroid and euthyroid states of the same patients. The eGFR was calculated using the simplified modification of diet in renal disease (MDRD) Formula. Among these patients, 367 had overt, and 66 had subclinical hyperthyroidism. fT3, fT4, and eGFR measurements decreased, meanwhile BUN, creatinine and TSH levels increased significantly after euthyroidism was achieved (p < 0.0001 for all). The correlation analyses revealed that eGFR in hyperthyroid state (eGFRh) and fT3 in hyperthyroid state (fT3h) (r = 0,210, p < 0,0001), and fT4 in hyperthyroid state (fT4h) (r = 0,176, p < 0,0001) were significantly correlated. ∆GFR did not differ between overt hyperthyroid group and subclinical hyperthyroid group. We observed a significant decline in eGFR measurements after the patients became euthyroid. Some of these patients had lower values than 60 mL/min/1.73 m2, which mean that hyperthyroidism may be masking mild renal failure.

Pharmacokinetics and toxicity of high-dose baclofen in ICU patients

BackgroundHigh-dose baclofen could prove beneficial in patients with unhealthy alcohol use in intensive care units (ICU). However, the pharmacokinetic properties of baclofen are unknown in this population. Our objectives were to investigate the pharmacokinetics of baclofen and the relationship between baclofen exposure and its toxicity in the ICU. Materials and methodsAs part of a healthcare quality improvement project, we conducted a prospective, single-center study in a surgical intensive care unit at Nantes University Hospital in order to assess our local protocol of sedation in patients with consumption of alcohol above the recommended limits by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Baclofen pharmacokinetics were investigated by a non-compartment analysis and a population approach in 20 patients under mechanical ventilation. After a baclofen loading dose on day 1, daily doses were divided into 3 intakes adapted to glomerular filtration rate (GFR) and blood samples were withdrawn on day 3 for pharmacokinetic analysis. Baclofen was administered until extubation or tracheostomy and agitation-related events as well as the potential side effects of baclofen were noted. ResultsIn this population, pharmacokinetic parameters [absorption latency time = 0.37 h, absorption constant rate = 2.2 h−1, apparent volume of distribution = 105 L, apparent clearance (l/h) = 13.5 × (GFR/103)0.839] were characterized by modified absorption and the influence of renal function: renal failure significantly increased baclofen exposure (p = .007) and significantly decreased baclofen clearance (p = .007) compared with patients without renal failure. When comparing patients with or without possible signs of baclofen toxicity, no difference was found regarding baclofen exposure (p = .34) and plasma peak concentration (p = .26). ConclusionsThe a priori planned algorithm for dose adaptation according to renal clearance appeared to be suitable in our population. Daily administration of 150 mg of baclofen in ICU patients with preserved renal function did not lead to toxic concentrations in the plasma. A dose reduction of approximately 40%, 60% and 70% in patients with mild, moderate and severe renal failure could be suggested.

Successful treatment of idiopathic retroperitoneal fibrosis with combined immunosuppressive therapy

Background/Aim. Idiopathic retroperitoneal fibrosis (IRF) is characterized by the fibroinflammatory periaortic tissue that affects the ureters, causing obstructive nephropathy and variable impairment of renal function. The findings strongly suggest an autoimmune etiology. The optimal treatment has not been established. The aim of this study was to analyze a long-term efficacy of combined corticosteroid therapy with mycophenolate mofetil (MMF) in the patients with IRF. Methods. We retrospectively followed 13 patients (8 males and 5 females) with IRF. All patients received corticosteroids and MMF. For the patients with severe renal failure, an initial ureteral decompression was made and prednisone was started orally 0.5 mg/kg with fast tapering. In cases with a mild renal failure corticosteroids were administrated as intravenous methylprednisolone pulses for 3 days, followed by oral prednisone. The dose of MMF was 1000 mg twice a day. MMF was stopped after 18 months and prednisone after 48 months. Results. Systemic symptoms resolved in all patients. Erythrocyte sedimentation (SE) rate declined from the mean of 67.6 to 26.3 mm/h and C-reactive protein (CRP) from the mean of 18.5 to 6.3 mg/L. In 7 out of 8 patients, the ureteral stents were successfully removed 13 weeks on average. Seven patients had 100% of reduction in the periaortic mass, and the average percent reduction was 76.9%. The kidney function improved and remained normal in 6 treated patients. In 4 patients a mild chronic renal failure remained due to afunction of one kidney. Three patients, with a prior chronic renal failure, did not get worse renal function. The disease recurred in 3 patients. There were no treatment side effects noted. Conclusion. Combination of corticosteroids and MMF is a potentially effective treatment in restoring the renal function and reducing the fibrotic tissue in the patients with idiopathic retroperitoneal fibrosis. It could prevent the need for ureteral stenting and surgery. Longer treatment may reduce a possibility of recurrence.

Heavy chain disease: a rare case report of adult nephrotic syndrome

Monoclonal immunoglobulin deposition disease is a systemic disorder characterized by the deposition of immunoglobulins as nonfibrillar material in various organs. Three subtypes have been reported: light chain deposition disease, light and heavy chain deposition disease and heavy chain deposition disease. Among these, light chain deposition disease is the most prevalent. Reports of light and heavy chain and heavy chain disease are rare, with fewer than two dozen documented cases in the world literature and very few from India. Heavy chain disease is characterized by glomerular, tubular, and vascular wall deposition of monoclonal heavy chains without associated light chains. We present the case of a 51-year man, who presented with a 3-month history of pedal edema, hypertension detected 3 months ago, and mild renal failure Estimated Glomerular filteration rate (eGFR) 66 ml/min/1.73 m2; histopathology showed heavy chain deposition disease. The case emphasizes the need for a thorough workup for plasma cell dyscrasias when we see membranoproliferative pattern in adult patients. This patient was treated with bortezomib-based regimen and after 3 months achieved near-complete remission of proteinuria with improvement in serum creatinine.

Safety and Efficacy of DPP4 Inhibitor and Basal Insulin in Type 2 Diabetes: An Updated Review and Challenging Clinical Scenarios.

The safety and efficacy of dipeptidyl peptidase-4 (DPP4) inhibitors as monotherapy or in combination with other oral antidiabetic agents or basal insulin are well established. DPP4 inhibitors stimulate glucose-dependent insulin secretion and inhibit glucagon production. As monotherapy, they reduce the hemoglobin A1c level by about 0.6–0.8%. The addition of a DPP4 inhibitor to basal insulin is an attractive option, because they lower both postprandial and fasting plasma glucose concentrations without increasing the risk of hypoglycemia or weight gain. The present review summarizes the extensive evidence on the combination therapy of DPP4 inhibitors and insulin-based regimens in patients with type 2 diabetes. We focus our discussion on challenging clinical scenarios including patients with chronic renal impairment, elderly persons and hospitalized patients. The evidence indicates that these drugs are highly effective and safe in the elderly and in the presence of mild, moderate and severe renal failure improving glycemic control with low risk of hypoglycemia. In addition, several randomized-controlled trials have shown that the use of DPP4 inhibitors in combination with basal insulin represents an alternative to the basal-bolus insulin regimen in hospitalized patients with type 2 diabetes.

P4397Effect of mild renal failure on admission on short- and long-term outcomes in patients with STEMI undergoing primary PCI

P4397Effect of mild renal failure on admission on short- and long-term outcomes in patients with STEMI undergoing primary PCI

Prevalence and risk factors of mild chronic renal failure in HIV-infected patients: influence of female gender and antiretroviral therapy

BackgroundIn people living with HIV, much is known about chronic kidney disease, defined as a glomerular filtration rate under 60mL/min. However, there is scarce data about prevalence and risk factors for milder impairment (60–89mL/min). ObjectiveThe present study aims to assess the influence of sex, antiretroviral therapy, and classical risk factors on the occurrence of mild decreased renal function in a large Spanish cohort of HIV-infected patients. MethodsCross-sectional, single center study, including all adult HIV-1-infected patients under antiretroviral treatment with at least two serum creatinine measures during 2014, describing the occurrence of and the risk factors for mildly decreased renal function (eGFR by CKD-EPI creatinine equation of 60–89mL/min). ResultsAmong the 4337 patients included, the prevalence rate of mildly reduced renal function was 25%. Independent risk factors for this outcome were age older than 50 years (OR 3.03, 95% CI 2.58–3.55), female sex (OR 1.23, 95% CI 1.02–1.48), baseline hypertension (OR 1.57, 95% CI 1.25–1.97) or dyslipidemia (OR 1.48, 95% CI 1.17–1.87), virologic suppression (OR 1.88, 95% CI 1.39–2.53), and exposure to tenofovir disoproxil-fumarate (OR 1.67, 95% CI 1.33–2.08) or ritonavir-boosted protease-inhibitors (OR 1.19, 95% CI 1.03–1.39). ConclusionsFemales and patients over 50 seem to be more vulnerable to renal impairment. Potentially modifiable risk factors and exposure to tenofovir disoproxil-fumarate or ritonavir-boosted protease-inhibitors are present even in earlier stages of chronic kidney dysfunction. It remains to be determined whether early interventions including antiretroviral therapy changes (tenofovir alafenamide, cobicistat) or improving comorbidities management will improve the course of chronic kidney disease.

Cellular ciliary phenotyping indicates pathogenicity of novel variants in IFT140 and confirms a Mainzer\u2013Saldino syndrome diagnosis

BackgroundMainzer–Saldino syndrome (MZSDS) is a skeletal ciliopathy and part of the short-rib thoracic dysplasia (SRTD) group of ciliary disorders. The main characteristics of MZSDS are short limbs, mild narrow thorax, blindness, and renal failure. Thus far, variants in two genes are associated with MZSDS: IFT140, and IFT172. In this study, we describe a 1-year-old girl presenting with mild skeletal abnormalities, Leber congenital amaurosis, and bilateral hearing difficulties. For establishing an accurate diagnosis, we combined clinical, molecular, and functional analyses.MethodsWe performed diagnostic whole-exome sequencing (WES) analysis to determine the genetic cause of the disease and analyzed two gene panels, containing all currently known genes in vision disorders, and in hearing impairment. Upon detection of the likely causative variants, ciliary phenotyping was performed in patient urine-derived renal epithelial cells (URECs) and rescue experiments were performed in CRISPR/Cas9-derived Ift140 knock out cells to determine the pathogenicity of the detected variants in vitro. Cilium morphology, cilium length, and intraflagellar transport (IFT) were evaluated by immunocytochemistry.ResultsDiagnostic WES revealed two novel compound heterozygous variants in IFT140, encoding IFT140. Thorough investigation of WES data did not reveal any variants in candidate genes associated with hearing impairment. Patient-derived URECs revealed an accumulation of IFT-B protein IFT88 at the ciliary tip in 41% of the cells indicative of impaired retrograde IFT, while this was absent in cilia from control URECs. Furthermore, transfection of CRISPR/Cas9-derived Ift140 knock out cells with an IFT140 construct containing the patient mutation p.Tyr923Asp resulted in a significantly higher percentage of IFT88 tip accumulation than transfection with the wild-type IFT140 construct.ConclusionsBy combining the clinical, genetic, and functional data from this study, we could conclude that the patient has SRTD9, also called Mainzer–Saldino syndrome, caused by variants in IFT140. We suggest the possibility that variants in IFT140 may underlie hearing impairment. Moreover, we show that urine provides an excellent source to obtain patient-derived cells in a non-invasive manner to study the pathogenicity of variants detected by genetic testing.