Improvement In Renal Function Research Articles

Primary versus deferred ureteroscopy for the management of obstructive anuria secondary to ureteric urolithiasis in children: a prospective randomized study

To compare the role of primary and deferred ureteroscopy (URS) in the management of obstructive anuria secondary to ureteric urolithiasis in pediatric patients. This prospective randomized study included 120 children aged ≤ 12 years who presented with obstructive anuria secondary to ureteric urolithiasis between March 2019 and January 2021. The children were subdivided into group A, which included children who had undergone primary URS without pre-stenting, and group B, which included children who had undergone URS after ureteric stenting. All children were clinically compensated and sepsis-free. Patients with underlying urological structural abnormalities were excluded. The operative time, improvement of renal functions, stone-free rate, and complications were compared between the two groups. At the 1-month follow-up, urine analysis; kidney, ureter, and bladder radiography; and ultrasonography were performed. The patient characteristics of both groups did not show any significant difference. Primary URS had failed in ten children (16.6%) in group A. Moreover, failure of stenting was noted in six patients (11%) in group B. The mean operative time for group B was significantly lower than that for group A (p ≤ 0.001). The stone-free rate was significantly higher in group B (p ≤ 0.001). The rate of overall complications was higher in group A. Deferred URS is preferable over primary URS in the management of obstructive anuria secondary to ureteric urolithiasis”. In children because of the lower need for ureteric dilatation, higher stone- free rate, shorter procedure time, and lower complication rate.

Place de l’avacopan dans le traitement de la vascularite associée aux ANCA What role for avacopan in the treatment of ANCA-associated vasculitis?

Recent experimental data have revealed the complement, and more specifically the C5a compound, plays a major role in the pathophysiology of ANCA associated vasculitis (AAV). The development of avacopan, an oral inhibitor of C5a receptor, has allowed to test the blockade of this immunological pathway, initially in a murine animal model of the disease, followed by a preliminary, phase 2 therapeutic trial in human disease, with promising results. An international phase 3 trial published in 2021 demonstrated that avacopan can be used instead of corticosteroids for the induction therapy of AAV, in association with an immunosuppressive drug such as cyclophosphamide or rituximab. The adjunction of this new-generation immunosuppressive drug does not increase the infectious risk, but seems to amplify the improvement of renal function during the initial treatment of renal vasculitis. These results have led to the recent registration of avacopan, opening new therapeutic options in AAV. © 2022 Published by Elsevier Masson SAS on behalf of Société francophone de néphrologie, dialyse et transplantation.

Yiqi Huoxue Tongluo recipe regulates NR4A1 to improve renal mitochondrial function in unilateral ureteral obstruction (UUO) rats

Context Yiqi Huoxue Tongluo recipe (YHTR) is a traditional Chinese medicine for the treatment of chronic kidney disease, but its exact mechanism is not clear. Objectives To monitor the potential improvement of renal mitochondrial function in unilateral ureteral obstruction (UUO) rats by regulating NR4A1 using the YHTR. Materials and methods Wistar rats were randomly divided into four groups: sham, UUO (left ureteral ligation for 14 days), eplerenone (EPL) (UUO + EPL), and YHTR (UUO + YHTR). UUO rats were established and intragastrically administered EPL (100 mg/day/kg) or YHTR (11.7 g/day/kg) for 14 days. The expression of related proteins in kidneys was detected by immunohistochemistry, western blot, RT-PCR, and chemical colorimetric assay, respectively. Results In vivo, YHTR treatment reduced the levels of BUN and Scr (by 17.9% and 23.5%) in UUO rats. Moreover, YHTR improved the renal mitochondrial function via increasing key enzymes of the tricarboxylic acid (TCA) cycle (p < 0.05) and activity of the mitochondrial complex (I–V) (by 30.8%, 29.1%, 19.7%, 35.9%, and 22.4%) in UUO rats. Compared with the UUO group, the expression of NR4A1 and Bcl-2 were significantly increased (p < 0.05), the expression of caspase-3 and caspase-9 were significantly decreased (p < 0.05) in the YHTR group. YHTR could upregulate key enzymes of the TCA cycle via promoting NR4A1 expression in HK2 cells, leading to inhibition of TGF-β1 induced cell apoptosis. Conclusions YHTR significantly improved the development of CKD; this study may provide new ideas for the pathogenesis of CKD and new strategies for the development of new drugs against CKD.

A Rare Case of Spontaneous Tumor Lysis Syndrome As a Consequence of Forgone Treatment in Multiple Myeloma

Being diagnosed with cancer comes with numerous challenges and tumor lysis syndrome (TLS) is just one of many complications a cancer patient may be faced with while undergoing treatment. This is considered an oncologic emergency that occurs when large amounts of tumor cells rapidly break down and release phosphate, potassium, lactate dehydrogenase, and nucleic acids into the bloodstream. The majority of cases are associated with treatment in acute lymphoblastic leukemia and high-grade lymphoma, although it can occur in other instances of cancer with a large tumor burden, high proliferative rate, and even rarer, may occur spontaneously in the absence of those features. A 55-year-old male with a past medical history of COPD, coronary artery disease status post CABG, heart failure with reduced ejection fraction, type 2 diabetes mellitus, hypothyroidism, and multiple myeloma was transferred to our facility for further workup of acute encephalopathy and severe hypercalcemia. He was initially taken to an outside hospital by family members after they noticed he became disoriented and lethargic over the course of a couple of days. His family also noticed he was gradually becoming weaker and experienced a 30-pound unintentional weight loss over the course of the month and a half following his discharge from the hospital after undergoing CABG. Labs were drawn upon admission and were significant for a critical calcium level of 16.4 mg/dL, PTH 6.7 pg/mL, creatinine 2.49 mg/dL, and ammonia 105.0 uMOL/L. Myeloma labs showed M spike of 4.7 g/dL, IgA of 6147 mg/dL with Kappa light chains of 1086 mg/L with a ratio of 221. When asked about his multiple myeloma diagnosis and treatment he was unable to provide much information, but our local oncology team was able to contact his home oncologist who informed us he had been diagnosed 2 years prior to this admission. He underwent a bone marrow transplant but chose to forgo any further treatment and was not following up regularly with his oncologist. The hypercalcemia was attributed to his malignancy and treated on arrival to the hospital with IV fluids, zoledronic acid, and calcitonin with a favorable response. He was continued on calcitonin until resolution of severe, symptomatic hypercalcemia. A uric acid level ordered the following morning came back at a critical value of 16.2 mg/dL. At that time, he was diagnosed with spontaneous tumor lysis syndrome and was immediately treated with 6 mg rasburicase followed by daily 300 mg allopurinol. Chemotherapy was initiated while inpatient and he received two rounds of bortezomib/cyclophosphamide therapy prior to discharge. He remained hospitalized for nine days with significant clinical improvement and on the day of discharge labs showed a calcium level of 6.6 mg/dL, improvement in renal function with creatinine down to 2.09 mg/dL, and uric acid level 4.5 mg/dL. He was set up with close outpatient follow-up with his home oncologist and plans to continue this chemotherapy regimen. Although not uncommon, in more recent years there has been a trend downward in the incidence of tumor lysis syndrome thanks in part to better prevention methods and early recognition. For multiple myeloma specifically, the risk of tumor lysis syndrome is actually less than one percent and the risk of spontaneous TLS is likely even rarer. The actual incidence of developing spontaneous TLS, in general, is difficult to predict and in multiple myeloma other than a few case reports, it has not been widely documented. The goal of sharing this case is to contribute to the information already known about this condition and hopefully encourage others to share similar cases to improve recognition for earlier treatment and lower morbidity and mortality associated with spontaneous TLS in the future.

Idiopathic Multicentric Castleman's Disease with Concurrent Renal Involvement

Introduction Castleman Disease (CD) is a rare non-clonal benign lymphoproliferative disease.CD can be classified into various subtypes based on etiology, clinical and histological findings. Management of CD varies based on the diagnosis and patient's condition and it can range from surgical excision to more aggressive systemic therapies such as anti-IL-6, steroids, and chemotherapy. It can rarely present with renal involvement, which is poorly understood. Case Presentation A 31-year-old male patient with a history of hospital admission one month prior to the present illness for persistent abdominal pain, with an incidental finding of splenomegaly and generalized lymphadenopathy on imaging, was admitted to the hospital for a 2-week history of generalized swelling with associated 20-pound weight gain, poor oral intake, nausea, vomiting, and loose stools. Laboratory work-up (TABLE 1) revealed hyponatremia with sodium of 117 mmol/L and renal failure with a creatinine of 1.6 mg/dL. Urinalysis showed proteinuria of 2+ and 24-hour collection revealed 300 mg of total protein. Heart failure was not noted on echocardiogram and biochemical or imaging findings were not suggestive of liver cirrhosis. Fluid restriction and diuretics were initiated. The patient improved initially but his hospital course was complicated by worsening renal failure and normochromic, normocytic anemia. Nephrology, Gastroenterology, Pulmonology, and Surgery were consulted. Excisional lymph node biopsy was performed revealing multicentric Castleman's Disease, negative for HHV-8. A kidney biopsy was performed later, consistent with thrombotic microangiopathy (Figure 1). VEGF and IL-6 were elevated. Hemodialysis was entertained,steroids were started, and Siltuximab was ordered but could not be obtained at the institution. Tocilizumab was started instead. The patient had a dramatic improvement after the treatment initiation and a week later the patient was discharged home. The patient's renal function was back to baseline and he was asymptomatic during the one-month follow-up visit. Discussion CD is a rare lymphoproliferative disease and renal involvement in CD is even rarer. There is still no consensus on how to manage CD patients with renal involvement. Here, we present an iMCD-NOS patient with renal involvement. Given the different therapeutic approaches, a final diagnosis of CD subgroups is important. The diagnosis of TAFRO, a rare clinicopathologic variant of idiopathic multicentric Castleman disease characterized by thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly was under consideration but discarded due to the patient lacking thrombocytopenia and it was decided to classify the patient under the not otherwise specified category. Renal complications from CD are uncommon and can include a variety of histopathological findings on biopsy, including thrombotic microangiopathy and membranoproliferative glomerulonephritis, among others.Our patient had thrombotic microangiopathy based on the renal biopsy findings. The pathophysiology of CD is not well understood. It is well known that IL-6 plays a role as increased levels of this proinflammatory marker have been associated with disease activity. Interestingly, increased serum levels of IL-6 and other cytokines have been observed in patients with several diseases characterized by renal thrombotic microangiopathy. Therefore, we hypothesize that increased IL-6 levels in patients with CD create an unhealthy environment for the renal microarchitecture that may result in thrombotic microangiopathy. As demonstrated by our case, improvement of renal function can be achieved after treating this pro-inflammatory state with systemic therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prospective Self-Control Analysis of Glucocorticoid Maintenance Therapy for Paroxysmal Nocturnal Hemoglobinuria

Background Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, complement-mediated hemolytic anemia caused by a somatic phosphatidylinositol glycan class A (PIGA) gene mutation on the X chromosome of hematopoietic stem cells. The mutation of PIGA gene destroys the biosynthesis of glycosylphosphatidylinositol (GPI), resulting in the lack of GPI anchor proteins, including CD55 and CD59 molecules, in hematopoietic stem cells and their progeny cells (erythrocytes, granulocytes, monocytes, lymphocytes). Erythrocyte membrane without CD55 and CD59 are prone to complement attack and lysis[1]. PNH presents as hemolytic anemia, bone marrow failure, and thrombosis, and so on. Targeting the terminal complement inhibitor, such as eculizumab (C5 inhibitors), could not only control hemolytic anemia, reduce thrombosis and transfusion, improve the staging status of chronic kidney disease, and prevents the deterioration of renal function in PNH patients. However, eculizumab has not yet been available in mainland of China, glucocorticoids is still used as the first-line therapy in China. Methods From September 2020 to April 2022, 26 PNH patients with high disease activity (HAD) were enrolled in the study. Oral prednisone was initiated at a dose of 1mg/kg/day and gradually tapered four weeks later. Clinical characteristics of patients was described in Table 1. Results The hemoglobin paired T-test results before treatment and at 1 month, 3 months, and 6 months after treatment were as follows: (69.12±14.83) vs (77.50±18.11), p＜0.05；(69.12±14.83) vs (74.15±18.23), p=0.15；(69.12±14.83) vs (75.54±19.91), p=0.09; paired chi-square test (McNemar Test) for anemia stratification (>90g/L, 60-90g/L, <60g/L) showed no marked changes: p=0.082, p=0.344, p=0.247; By Friedman Test, it showed reticulocyte percentage was also similar: (6.76±3.92) vs (6.23±4.08) vs (6.62±3.92) vs (7.11±4.73), p=0.457. Before treatment, 25 patients (25/26, 96.15%) were transfusion dependent. After treatment at 1 month, 3 months, 6 months, 19 patients (19/26, 73.08%), 22 patients (22/26, 84.62%), 21 patients (21/26, 80.77%) were transfusion dependent, respectively (p=0.031; p=0.375; p=0.219). Two patients progressed to transfusion dependent at 3 months, 6months, respectively. No patients achieved remission of hemolysis (LDH < 1.5 ⅹULN) at 1, 3, and 6 months; the level of lactate dehydrogenase and indirect bilirubin (IBIL) showed no changes by analysis with Friedman test (p=0.436, p=0.881). By Friedman test, the serum level of D-dimer also showed no changes at different times ( p=0.263). Level of D-dimer elevated (>0.55mg/L) in seven patients before treatment, and returned back within normal range in one patient at 1 month, two patients at 3 months, three patients at 6 months. But among the people with normal D level initially, one patient and three patients each had elevated D-dimer level at 3 months and 6 months, respectively. Two patients achieved renal function improvement at 3 months, 6months, respectively. But three patients had renal function deterioration after treatment. Glomerular filtration rate (GFR) was (114.15±42.98) ml/min/1.73m2 before treatment, and become (117.79±37.69) ml/min/1.73m2, (120.85±44.05) ml/min/1.73m2, (110.30±36.58) ml/min/1.73m2 at 1, 3, and 6 months (p=0.42, p=0.43, p=0.41). Discussion Previous studies have mainly compared the improvement of anemia after breakthrough of PNH by glucocorticoids therapy. The improvement of anemia could not be ruled out as a result of transfusion support or the reduction of temporary hemolysis after breakthrough of PNH. We found the level of LDH increased along with improvement of hemoglobin during prednisone treatment, and percentage of reticulocytes was not changed at same time. It suggested that the improvement of anemia in some patients may not be caused by controlling intravascular hemolysis or the compensatory hyperplasia of the bone marrow, but by transfusion. Conclusions It preliminarily showed prednisone maintenance therapy for PNH could not control hemolysis and thrombosis, and could not improve anemia and renal function. The efficacy of glucocorticoid maintenance therapy in PNH is uncertain. Reference: [1] Brodsky R A. How I Treat Paroxysmal Nocturnal Hemoglobinuria[J]. Blood, 2021, 137(10): 1304-1309. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 11363: Renal Artery Velocity Time Integral is a Predictor of Improvement in Renal Function After Transcatheter Aortic Valve Implantation

Background: It has been reported that renal function (RF) is improved in a certain number of patients who undergo TAVI. However, the mechanisms and predictors of RF improvement remain unclear. We investigated whether preoperative renal hemodynamics assessed by intrarenal doppler ultrasonography (IRD) could predict RF improvement after TAVI. Methods and Results: We enrolled consecutive 84 patients with severe aortic stenosis (AS) who underwent TAVI in our hospital. To assess preoperative intrarenal hemodynamics, we measured renal artery velocity time integral (RA-VTI) as a marker of renal perfusion and renal venous stasis index (RVSI) as a marker of renal congestion using IRD before TAVI (Fig 1). We calculated RVSI as follows: (cardiac cycle time - venous flow time)/cardiac cycle time. RF improvement was defined as an increase &gt;10% of estimated glomerular filtration rate (eGFR) after TAVI. Of the 84 patients, 45 patients (53.5%) showed RF improvement and remaining 39 patients did not. Clinical characteristics including STS score, clinical frailty scale, comorbidities, medications, amount of contrast media and occurrence of procedural complications associated with TAVI were comparable between the two groups. In addition, laboratory data including baseline eGFR and echocardiographic parameters including severity of AS, left ventricular ejection fraction and stroke volume index were also similar between the two groups. RA-VTI determined by IRD was significantly lower in patients with RF improvement compared to those without RF improvement (34.0 ± 12.6 vs. 39.9 ± 12.5 cm, P=0.03). In contrast, there was no difference in RVSI (0.08 ± 0.13 vs. 0.05 ± 0.09, P=0.19). Logistic regression analysis indicated that RA-VTI was a predictor for RF improvement after TAVI (odds ratio 0.96, 95% confidence interval 0.93-0.99, P=0.04). Conclusions: Preoperative RA-VTI, a marker of renal perfusion, is a predictor for RF improvement after TAVI.

Effects of Ziyin Qianyang Formula on Renal Fibrosis through the TGF-β1/Smads Signaling Pathway in Spontaneously Hypertensive Rats.

The aim of the study is to explore the effects and mechanisms of action of Ziyin Qianyang Formula (ZYQYF) on renal fibrosis in spontaneously hypertensive rats (SHRs). Forty SHRs were randomly divided into a model group, Ziyin Qianyang Formula regular-dose and high-dose groups (ZYQYF-R, 20 g/kg; ZYQYF-H, 40 g/kg), and a western medicine group (enalapril 10 mg/kg), and 10 Sprague-Dawley rats were selected as the normal group. The rats received continuous gavage administration for 6 weeks and systolic blood pressure (SBP) measurements were obtained every fortnight. The serum levels of urea, serum creatinine (sCr), and uric acid (UA) were measured; the pathological morphology and collagen content of the kidneys were observed by hematoxylin-eosin (HE) and Masson staining; and the serum Ang II level was measured by an enzyme-linked immunosorbent assay (ELISA). Transforming growth factor (TGF)-β1, Smad-2, Smad-3, and Smad-7 protein and mRNA expressions in kidney tissues was evaluated by western blotting and reverse transcription-polymerase chain reaction. The ZYQYF-H group showed significantly a lower renal weight and renal weight/body weight than the model group. The enalapril and ZYQYF-H groups showed significantly lower SBP than other groups after 6 weeks of administration. The ZYQYF-H group showed better improvement than the ZYQYF-R and enalapril groups in glomerular and tubular morphology and better reductions in inflammatory cell infiltration and collagen volumetric fraction. The ZYQYF-H group also showed better reductions in serum UA and Ang II levels; collagen-I, collagen-III, and p-Smad2/Smad-2 protein expression; and Smad-2 mRNA expression and a better increase in Smad-7 protein and mRNA expression than the enalapril group. Besides, the degree of renal function and fibrosis improvement was positively correlated with the dose of ZYQYF. ZYQYF can significantly reduce SHR blood pressure, protect renal function and structure, and improve renal fibrosis by regulating Smad proteins through TGF-β1.

Letter to the Editor Regarding "Improvement of Renal Function After Bariatric Surgery: a Systematic Review and Meta‑Analysis".

Letter to the Editor Regarding "Improvement of Renal Function After Bariatric Surgery: a Systematic Review and Meta‑Analysis".

Paraproteinämien und Nierenbeteiligung

Renal manifestations in patients with monoclonal paraproteinemia are frequent. Cast nephropathy is a disease that only occurs in manifest multiple myeloma with a high tumor burden. In contrast, monoclonal gammopathy of renal significance (MGRS) is defined as renal involvement due to a nephrotoxic clone that from a hematological standpoint would per se not require treatment. The diagnosis of MGRS can only be made by renal biopsy. Here monotypic immunoglobulin (Ig) deposits can be found in either organized (amyloidosis, fibrillary glomerulonephritis, GN, immunotactoid GN, cryoglobulinemic GN) or nonorganized forms (monoclonal Ig deposition disease, proliferative GN with monoclonal Ig deposits). There are two forms of MGRS that can occur without the deposition of Ig, namely C3 glomerulopathy and thrombotic microangiopathy. For cast nephropathy there is always a fundamental indication for chemotherapy. The data on mechanical elimination of light chains by plasmapheresis or high cut-off dialysis are inconsistent. In patients with MGRS the indications for treatment must be made based on the renal prognosis in a cooperation between nephrologists and hematologists. Only a clone-directed treatment can lead to an improvement of renal function.

PSUN265 Metformin-Induced Severe Lactic Acidosis Requiring Urgent Dialysis Associated With Influenza A Infection in a Patient With Previous Preserved Renal Function: Case Report

Abstract Background Although rare, metformin-induced lactic acidosis it's a severe acute condition, that requires immediate recognition and management due to its high lethality. Clinical case Female, 70-years-old, presents to the E.R. with generalized malaise, weakness and myalgia for 4 days associated with diarrhea and vomits for 2 days. Denies fever or flu-like symptoms. History of hypertension and T2DM using metoprolol 100mg/day, perindopril 10mg/day, indapamide 2.5mg/day, amlodipine 5mg/day, linagliptin 5mg/day, rosuvastatin 10mg/day, gliclazide 120mg/day, aspirin 100mg/day, clonidine 0.3mg/day and metformin XR 1g/day. On clinical exam she was dehydrated and tachypneic with no other important findings. Laboratory showed glucose 31mg/dL, severe metabolic acidosis - pH 6,0; HCO3 5,4mmol/L; lactate 11.6mmol/L (n&amp;lt;1.6mmoL/L), acute renal failure KDIGO 3, creatinine 8.08mg/dL eGFR 5mL/min/1.73m2 (patient's baseline 0.9mg/dL), BUN 213mg/dL (n&amp;lt;50mg/dL), potassium 6.8mEq/L (3.5&amp;gt;n&amp;lt;5.1mEq/L), phosphor 14.9mg/dL (2.7&amp;gt;n&amp;lt;4.5mg/dL), chlorine 92mEq/L (98&amp;gt;n&amp;lt;107mEq/L), magnesium 1.7mg/dL (1.6&amp;gt;n&amp;lt;2.6mg/dL), calcium 0.95mmol/L (1.16&amp;gt;n&amp;lt;1.32mmol/L), and normal blood count. She was admitted to the ICU, hemodynamically stable with no need for vasoactive amine, breathing under nasal cannula and proceed with emergency hemodialysis. Acidosis was corrected after 6h of hemodialysis. Patient turned eupneic in room air and presented renal function improvement (BUN 44mg/dL; Creatinine 2.66mg/dL). She continued under intensive care and daily hemodialysis for another 4 days. The etiological investigation excluded glomerulopathies of rheumatological cause, blood cultures, serology for hepatitis, HIV and Dengue were all negative. However, respiratory viral panel was positive for influenza A. Although metformin serum dosage was not performed, renal function stability without the need for hemodialysis was only achieved after discontinuation of metformin. The main diagnostic hypothesis was metformin-induced severe metabolic acidosis. Finally, the patient was discharged on day 10, with stable renal function without hemodialysis (creatinine 2.19mg/dL eGFR 22mL/min/1.73m2) and no neurological deficits. The patient was referred to the endocrinologist and nephrologist to follow-up. Conclusion Metformin is affordable, safe and widely prescribed since the 50's. Although rare, metformin-induced lactic acidosis is a lethal toxicity, with identifiable risk factors that must be considered by prescribers. References Lazarus, Benjamin et al. "Association of Metformin Use With Risk of Lactic Acidosis Across the Range of Kidney Function: A Community-Based Cohort Study." JAMA internal medicine vol. 178,7 (2018): 903-910. doi: 10.1001/jamainternmed.2018.0292 Salpeter, Shelley R et al. "Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus." The Cochrane database of systematic reviews vol. 2010,4 CD002967. 14 Apr. 2010, doi: 10.1002/14651858.CD002967.pub4 Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Effect of pegylated interferon-α2b add-on therapy on renal function in chronic hepatitis B patients: A real-world experience.

Controversy remains as to pegylated interferon-α (PEG-IFNα) antiviral therapy to renal function in chronic hepatitis B (CHB) patients. The aim of this study was to evaluate the influence of PEG-IFNα2b (Y shape, 40 kD) add-on treatment for renal function in CHB patients who received entecavir therapy. This was a retrospective observational study to investigate factors related to renal function in 114 CHB patients who received PEG-IFNα2b add-on therapy to entecavir for 48 weeks. Changes of blood urea nitrogen (BUN), serum creatinine (sCr), and estimated glomerular filtration rate (eGFR), which was calculated with both Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease (MDRD) formulas, were analyzed by one-way analysis of variance. A linear mixed effects model for repeated measures was used to assess the correlation between baseline information and eGFR changes at 24 and 48 weeks of therapy. The model considered the baseline age, gender, body weight, viral load, hepatitis B surface antigen, BUN, sCr, and treatment strategy as fixed effects and incorporated random effects for individual subjects. BUN and sCr was decreased, while eGFR was increased at 12 weeks of therapy. Only eGFR maintained at 24 and 48 weeks of therapy. Patients with female gender, age ≥ 40 years, and baseline HBsAg level < 250 IU/mL showed significant improvement of renal function with PEG-IFNα2b add-on therapy. The linear mixed effects model revealed that female gender, baseline sCr, and PEG-IFNα2b add-on were significant positive predictors for eGFR elevation at 24 and 48 weeks of therapy. In real-world experience, PEG-IFNα2b add-on therapy might be associated with increased eGFR in CHB patients.

The Beneficial Effects of Bariatric-Surgery-Induced Weight Loss on Renal Function.

Obesity represents an independent risk factor for the development of chronic kidney disease (CKD), leading to specific histopathological alterations, known as obesity-related glomerulopathy. Bariatric surgery is the most effective means of inducing and maintaining sustained weight loss. Furthermore, in the context of bariatric-surgery-induced weight loss, a reduction in the proinflammatory state and an improvement in the adipokine profile occur, which may also contribute to the improvement of renal function following bariatric surgery. However, the assessment of renal function in the context of obesity and following marked weight loss is difficult, since the formulas adopted to estimate glomerular function use biomarkers whose production is dependent on muscle mass (creatinine) or adipose tissue mass and inflammation (cystatin-c). Thus, following bariatric surgery, the extent to which reductions in plasma concentrations reflect the actual improvement in renal function is not clear. Despite this limitation, the available literature suggests that in patients with hyperfiltration at baseline, GFR is reduced following bariatric surgery, whereas GFR is increased in patients with decreased GFR at baseline. These findings are also confirmed in the few studies that have used measured rather than estimated GFR. Albuminuria is also decreased following bariatric surgery. Moreover, bariatric surgery seems superior in achieving the remission of albuminuria and early CKD than the best medical treatment. In this article, we discuss the pathophysiology of renal complications in obesity, review the mechanisms through which weight loss induces improvements in renal function, and provide an overview of the renal outcomes following bariatric surgery.

Response and Dynamics of Renal Function in Transplantation-Eligible Multiple Myeloma Patients Treated with a Novel Agent: The CAREMM-2201 Study

Newly diagnosed multiple myeloma (NDMM) frequently results in renal impairment (RI), and its natural course has not been fully elucidated in the era of novel agents. We aimed to identify the dynamics of renal function after autologous stem cell transplantation (ASCT) following induction treatment using a novel agent in transplantation-eligible NDMM patients with RI (estimated glomerular filtration rate [eGFR] ≤50 mL/min/1.73 m2) at diagnosis. The factors associated with achieving a renal response based on the term renal benefit regardless of baseline eGFR were investigated as well. In a multicenter registry database including 1795 patients with plasma cell disorder, 140 transplantation-eligible NDMM patients who developed RI at the time of initiation of treatment for NDMM were identified. They received protocol-based treatment (PBT) consisting of induction treatment using proteasome inhibitors and/or immunomodulatory drugs followed by ASCT. MM and renal responses were evaluated using the International Myeloma Working Group response criteria. To evaluate the standardized improvement of renal function irrespective of baseline eGFR, renal benefit was defined as a sustained (for at least 3 months) increase in eGFR >15 mL/min/1.73 m2. The mean patient age was 54.7 ± 7.4 years. With a mean baseline eGFR of 24.8 ± 13.9, the renal complete response (renalCR) and renal benefit rates were 49.3% and 67.9%, respectively. In a multivariable analysis, the 3 factors significantly associated with reduced likelihood of achieving both renalCR and renal benefit were age ≥55 years, light chain type NDMM, and failure to improve eGFR by 5 mL/min/1.73 m2 with supportive care when measured 3 days prior to induction therapy and at the initiation of chemotherapy. Hypertension and advanced eGFR also were associated with poor renalCR achievement. The mean eGFR improved until the time of ASCT and then decreased gradually over time. The mean eGFR improved significantly until 4 months post-PBT compared with each eGFR at previous time points, but this significant improvement disappeared by 5 months post-PBT. In a subgroup of patients who developed RI after undergoing ASCT (n=55), the eGFR increased temporarily at 1 month post-ASCT; however, this improvement reverted to baseline at 2 months post-ASCT. Among another subgroup of 27 patients who were dialysis-dependent at the time of initial treatment, 18 (66.7%) were no longer dialysis-dependent after a median of 60 days. The best renal response was acquired early during the PBT period, and ASCT did not have a robust impact on the renal outcome. Patients who failed to achieve a renal benefit should be provided with the best supportive care for chronic kidney disease, and this simplified criterion for evaluating the renal response needs to be validated in larger studies before it can be recommended. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Transthoracic echocardiography guidance of transcatheter edge-to-edge percutaneous tricuspid valve repair: the TTE-TTVR pilot study and methodology proposal

Abstract Background Transcatheter tricuspid valve repair (TTVR) is an emerging option for treating high-grade tricuspid regurgitation (TR) [1], mostly performed by edge-to-edge repair, and always guided by transesophageal echocardiography (TOE). In patients with excellent acoustic window, transthoracic echocardiography (TTE) can also provide a comprehensive understanding of tricuspid valve (TV) morphology [2]. Also, in TTVR there is no need for transseptal puncture. Purpose We sought to determine if TTVR can be successfully conducted by a novel TTE guiding approach, in conjunction with fluoroscopy [3]. Methods 30 consecutive patients, scheduled for TTVR, were assigned to a TTE group (n=10), in the presence of excellent acoustic window, and a TOE group (n=20). On top of fluoroscopy, TTVR was guided exclusively by TTE in the first group, with TOE result confirmation solely upon clip release, due to safety reasons. The second group underwent classical TOE guidance. Understanding the 4 right heart chamber views (Fig. 1) and their respective fluoroscopic angulations was paramount. TR severity, parameters of quality of life and functional capacity were assessed and compared between-groups, at baseline and 30 days. Results Except for lower BMI (TTE 22.3±0.8 vs TOE 29.8±4.3, p&amp;lt;0.001), other baseline characteristics were very similar between groups, e.g., age (81.7±3.9 vs 82.8±4.1, p=0.483) or EuroSCORE II (11.9±10.3 vs 10.4±8, p=0.692).Device success was achieved in all patients, with a total of 15 implanted clips in the TTE group (mean no. of clips / patient 1.5±0.7) and 31 clips in the TOE group (1.5±0.6). Device time (75±37.1 vs 65.7±31.3 minutes, p=0.506) and fluoroscopy duration (16.3±10.5 vs 14.4±7.2 minutes, p=0.564) were also close. TR reduction was successful in all but one patient, in each group (90% vs 95%, p=1.000). TR improvement was equal between-groups, with 2 or more grade reduction in 60% of each group, at 30 days. Thus, grade IV/V and V/V TR, present in 60% of all patients at baseline, dropped to 10% (9/10 vs 18/20, p=1.000) by procedure end and follow-up (Fig. 2). No device associated complications occurred. By 30 days, there was one non-cardiac death and one major bleeding. At follow-up, all but one patient had at least one grade reduction in NYHA class (10/10 vs 19/20, p=1.000). Kansas City Cardiomyopathy Questionnaire score and 6-minute walk distance similarly improved (Δ20.7±14.9 vs 15.5±7.9 points, p=0.227; Δ80.5±60.1 vs 46.6±30.6 meters, p=0.121). A statistical in-group difference was also noticed in renal function improvement by follow-up [glomerular filtration rate (GFR) TTE group 56.8±18.7 vs 64.8±12.5 ml/m2/1.73 m2, p=0.028; TOE group 50.7±19.9 vs 62.2±25.9, p=0.001]. Conclusion TTE guidance of TTVR is feasible in selected patients with excellent acoustic window and could offer an alternative in case of high anesthetic risk. Similar procedural success and clinical outcomes, as with TOE guidance, can be achieved. Funding Acknowledgement Type of funding sources: None.

SMALL VESSELS, BIG PROBLEMS: MICROSCOPIC POLYANGIITIS PRESENTING AS DIFFUSE ALVEOLAR HEMORRHAGE

SMALL VESSELS, BIG PROBLEMS: MICROSCOPIC POLYANGIITIS PRESENTING AS DIFFUSE ALVEOLAR HEMORRHAGE

DYSPNEIC AFTER EVERY COVID-19 SHOT: SUSPECTED BNT162B2 MRNA VACCINE-RELATED, DRUG-INDUCED PULMONARY EOSINOPHILIA

DYSPNEIC AFTER EVERY COVID-19 SHOT: SUSPECTED BNT162B2 MRNA VACCINE-RELATED, DRUG-INDUCED PULMONARY EOSINOPHILIA

S3707 A Cautionary Side of the Widely Prescribed: A Case of PPI-Induced AIN

Introduction: Proton pump inhibitors (PPIs) are widely prescribed for the treatment of gastric acid-related disorders. While generally well-tolerated, PPIs are not without side effects, including acute kidney injury. Here we highlight a rare case of biopsy proven PPI-induced acute interstitial nephritis (AIN). Case Description/Methods: A 54-year-old male with history of rheumatoid arthritis presented with one week history of fever, fatigue, arthralgias, and weight loss. One month prior he was admitted with upper GI bleeding due to NSAID induced peptic ulcer disease and promptly stopped NSAIDs with strict adherence to PPI therapy. He took no additional medications or supplements. On admission labs were notable for recurrent anemia without melena and new acute kidney injury, creatinine 2.32 mg/dL from baseline of 1. Given recent GI bleed patient underwent repeat EGD which showed a clean based healing antral ulcer. Recurrent anemia was attributed to renal dysfunction, which continued to worsen despite supportive care with peak creatinine 3.8 mg/dL. Urine studies were unrevealing without evidence of obstruction on imaging, but incidentally noted narrowing of the celiac artery was concerning for vasculitis related nephropathy given history of autoimmune disease. Confirmatory contrast enhanced imaging however was negative for evidence of vasculitis with negative serologies. Renal biopsy was performed which showed interstitial inflammation and tubulitis consistent with AIN. Ultimate diagnosis of PPI-induced AIN was made as he took no alternative medications which could be implicated. Patient was started on steroids with notable improvement in renal function. He was switched to an H2 receptor blocker to complete treatment of gastric ulcer and discharged on a steroid taper with complete renal recovery (Figure 1). Discussion: Initially described in 1992, PPI-induced AIN is a well-recognized albeit rare complication. It is thought to arise due to a hypersensitivity reaction, which may explain the classic presenting triad of fever, rash, and eosinophilia. However, studies have shown that this clinical triad is only present in 10% of cases thereby highlighting the difficulties of diagnosing AIN, which may ultimately require renal biopsy for definitive diagnosis. Treatment requires removal of the offending agent as well as initiation of steroids. Even with treatment, 30-70% of patients may develop chronic kidney disease. As such, it is important for clinicians to be cognizant of this potentially life altering complication of PPI.Figure 1.: Kidney biopsy showing inflammatory changes predominantly in the interstitium.

S2930 Calciphylaxis Due to Alcoholic Liver Disease

Introduction: Advanced liver disease often has multiorgan involvement, including dermatological findings. These range from spider angiomas to palmar erythema. Here we present a case of calciphylaxis as a manifestation of decompensated alcoholic liver disease. Case Description/Methods: A 38 year-old female with decompensated alcoholic cirrhosis (portal vein thrombosis, ascites, hepatic encephalopathy, and hepatic hydrothorax) reported to the emergency room complaining of new right thigh wounds. Her vital signs were unremarkable and her exam demonstrated ascites and bilateral lower extremity edema with right medial thigh erythema, induration, and superficial ulceration (Figure 1). Labs showed sodium 125 mEq/L, Creatinine 0.95 mg/dL, WBC 16.2 x109, and total bilirubin 1.6 mg/dL. CT of her thigh demonstrated bilateral, symmetric subcutaneous induration consistent with anasarca and possible superimposed cellulitis. She was admitted and treated with IV antibiotics. As the lesions became duskier and more painful dermatology was consulted who initially were concerned for a vasculopathic process versus calciphylaxis. The patient was placed on empiric treatment for calciphylaxis with sodium thiosulfate. Skin biopsies were performed and showed non-uremic calciphylaxis (Figure 2). The patient then developed an AKI thought to be from hepato-renal syndrome and was trialed on albumin, midodrine, and octreotide with no improvement in renal function. She then developed acidosis, eventually requiring a bicarb drip, and her wounds continued to progress (Figure 1). When she started becoming repeatedly hypotensive her family transitioned her to comfort care and she was discharged to hospice. Discussion: Calciphylaxis is a rare disease that was first described in 1961 by Selye et al and is largely thought to be related to uremia. Here we describe a case of calciphylaxis in a patient with alcoholic liver disease and initial normal renal function. Our review of the literature found fewer than 11 case reports of calciphylaxis associated with liver disease. The mechanism in these cases appears to be poorly understood though is believed to be connected to protein C and protein S deficiency. As in those with advanced renal disease, calciphylaxis has a poor prognosis with high mortality often reported as greater than 50% even despite treatment. Thus it is important that clinicians recognize its association with alcoholic liver disease to aid in diagnosis and ensure prompt initiation of treatment.Figure 1.: A: Right medial thigh wound B: High power of calcium deposits and thrombus (arrow) within the subcutaneous fat C: corresponding von kossa stain (arrowhead).

Does kidney function matter in pulmonary thromboembolism management?

Cardiovascular circulation and kidney function are closely interrelated. The impairment of renal function is a well-known hazard of increased mortality and morbidity of patients with heart failure or coronary artery disease. Acute pulmonary embolism (APE) impacts pulmonary and systemic circulation, and can severely impair functions of other organs, including kidneys, as a result of hypoxemia and increased venous pressure.Previous studies indicate that renal dysfunction predicts short- and long-term outcomes and can improve the risk assessment in APE. However, renal function should also be cautiously considered during the diagnostic workup because the contrast-induced nephropathy after computed tomography pulmonary angiography is noticed more frequently in APE. Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but imminent complication of APE. This condition promotes renal impairment by increasing venous pressure and decreasing glomerular filtration. The renal function improvement and serum creatinine concentration reduction were noted in CTEPH subgroup with glomerular filtration rate ≤ 60 mL/min/1.73 m2 after successful treatment.In this review, we present the essential research results on the kidney function in thromboembolism disease.