Kidney Recovery Research Articles

Diagnosing the Recent Decrease in Utilization of Deceased Donor Kidneys.

The number of deceased donor kidney transplants has been increasing and is at a record high, yet nonuse of kidneys recovered for transplantation has risen to 25.8% following circular kidney allocation system based on 250-nautical-mile circles implemented on March 15, 2021 (KAS250). Using Scientific Registry of Transplant Recipients data, we studied all deceased donor kidneys recovered for transplant from March 15, 2019, to January 31, 2023. We calculated the association of multiple factors with kidney nonuse, including increasing recovery of kidneys from nonideal donors, delays in offer acceptance observed under KAS250, and impacts of COVID-19. In the 2 y before KAS250, the nonuse rate was 21.2%. Had this rate continued, 2334 more kidneys would have been transplanted through January 2023. We estimated that about 769 of these nonused kidneys (33%) were associated with offer acceptance delays under KAS250; about 994 of these nonused kidneys (43%) were associated with increased prevalence of nonideal donors: donation after circulatory death donors, older donors, and donors with elevated peak serum creatinine; and about 542 of these nonused kidneys (23%) were associated with an otherwise unexplained gradual upward trend in nonuse of recovered kidneys across the pre-KAS250 and KAS250 eras. The overall impact of COVID-19 on the nonuse rate was not significant. The rise in kidney nonuse rate was significantly associated with both increased recovery of nonideal donors, and with KAS250 allocation complexity and delays. Increasing recovery of kidneys from nonideal donors benefits patients because recovering more kidneys increases the number of kidneys available for transplant.

Electronic Alert Systems for Patients With Acute Kidney Injury

The acute kidney injury (AKI) electronic alert (e-alert) system was hypothesized to improve the outcomes of AKI. However, its association with different patient outcomes and clinical practice patterns remains systematically unexplored. To assess the association of AKI e-alerts with patient outcomes (mortality, AKI progression, dialysis, and kidney recovery) and clinical practice patterns. A search of Embase and PubMed on March 18, 2024, and a search of the Cochrane Library on March 20, 2024, to identify all relevant studies. There were no limitations on language or article types. Studies evaluating the specified outcomes in adult patients with AKI comparing AKI e-alerts with standard care or no e-alerts were included. Studies were excluded if they were duplicate cohorts, had insufficient outcome data, or had no control group. Two investigators independently extracted data and assessed bias. The systematic review and meta-analysis followed the PRISMA guidelines. Random-effects model meta-analysis, with predefined subgroup analysis and trial sequential analyses, were conducted. Primary outcomes included mortality, AKI progression, dialysis, and kidney recovery. Secondary outcomes were nephrologist consultations, post-AKI exposure to nonsteroidal anti-inflammatory drugs (NSAID), post-AKI angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker (ACEI/ARB) prescription, hospital length of stay, costs, and AKI documentation. Thirteen unique studies with 41 837 unique patients were included (mean age range, 60.5-79.0 years]; 29.3%-48.5% female). The risk ratios (RRs) for the AKI e-alerts group compared with standard care were 0.96 for mortality (95% CI, 0.89-1.03), 0.91 for AKI stage progression (95% CI, 0.84-0.99), 1.16 for dialysis (95% CI, 1.05-1.28), and 1.13 for kidney recovery (95% CI, 0.86-1.49). The AKI e-alerts group had RRs of 1.45 (95% CI, 1.04-2.02) for nephrologist consultation, 0.75 (95% CI, 0.59-0.95) for post-AKI NSAID exposure. The pooled RR for post-AKI ACEI/ARB exposure in the AKI e-alerts group compared with the control group was 0.91 (95% CI, 0.78-1.06) and 1.28 (95% CI, 1.04-1.58) for AKI documentation. Use of AKI e-alerts was not associated with lower hospital length of stay (mean difference, -0.09 [95% CI, -0.47 to 0.30] days) or lower cost (mean difference, US $655.26 [95% CI, -$656.98 to $1967.5]) but was associated with greater AKI documentation (RR, 1.28 [95% CI, 1.04-1.58]). Trial sequential analysis confirmed true-positive results of AKI e-alerts on increased nephrologist consultations and reduced post-AKI NSAID exposure and its lack of association with mortality. In this systematic review and meta-analysis, AKI e-alerts were not associated with a lower risk for mortality but were associated with changes in clinical practices. They were associated with lower risk for AKI progression. Further research is needed to confirm these results and integrate early AKI markers or prediction models to improve outcomes.

Thoracoabdominal Normothermic Regional Perfusion Using Mobile Closed Extracorporeal Circuit in Circulatory Death Determination Heart Donors.

Thoracoabdominal normothermic regional perfusion (TA-NRP) is increasingly implemented in donation after circulatory determination of death (DCD). Thoracoabdominal normothermic regional perfusion allows thoracic and abdominal organs to be perfused with warm, oxygenated blood after declaration of death, interrupting ischemia. Evidence is accumulating supporting the use of TA-NRP to improve the outcome of grafts from DCD donors. Thoracoabdominal normothermic regional perfusion may restore and maintain a near-physiological environment during procurement. Moreover, during TA-NRP it is feasible to evaluate the heart in situ. Thoracoabdominal normothermic regional perfusion could be performed through different cannulation techniques, central or peripheral, and, with different extracorporeal circuits. The use of conventional cardiopulmonary bypass and extracorporeal life support (ECLS) devices equipped with open circuits has been described. We report the use of a fully mobile, closed ECLS circuit to implement TA-NRP. The procedure was successfully performed in a peripheral center without a cardiac surgery program through a percutaneous cannulation approach. This strategy resulted in combined heart, liver, and kidney recovery despite a significantly prolonged functional warm ischemia time. The feasibility of TA-NRP using modified but still closed fully mobile ECLS circuits could furtherly support the expansion of DCD programs, increasing the availability of heart for transplantation, and the quality of the grafts, improving recipients' outcome.

Association of Age, Frailty, and Strategy for Initiation of Renal-Replacement Therapy: A Post Hoc analysis of the STARRT-Acute Kidney Injury Trial

Plain Language SummaryThis study was designed to assess the association of age and frailty with clinical outcomes in patients with severe acute kidney failure using the data from an international randomized trial called the STARRT-AKI trial that examined the effect of timing of dialysis initiation on mortality in patients with acute kidney failure. In this study, older age was defined as ≥65 years, accounting for more than a half of the study population. This study demonstrated that older and frail patients carried higher mortality rates. However, age and frailty did not appear to have a significant impact on kidney recovery. Furthermore, in older or frail patients, timing of initiation of dialysis therapy did not affect mortality and kidney recovery. These findings will assist with triaging, prognostication, and management of older and frail patients with severe acute kidney failure in intensive care units.

Pomalidomide Use and Kidney Outcomes in Patients With Relapsed/Refractory Multiple Myeloma and Chronic Kidney Disease: A Real-World, Population-Based Cohort Study

BackgroundPomalidomide-based regimens are the cornerstone of treatment for relapsed/refractory MM (RRMM). Despite the high incidence of chronic kidney disease (CKD) in RRMM, individuals with advanced CKD have been excluded from phase II/III RCTs, creating a gap in our understanding of the effects of pomalidomide use in patients with RRMM complicated with advanced CKD. We undertook a cohort to study to understand the efficacy safety of pomalidomide-based regimens among patients with CKD using real-world data. MethodsPopulation-based, cohort study of patients ≥ 18 years with RRMM treated with pomalidomide in Ontario, Canada. Primary outcome was all-cause mortality. Secondary outcomes were time-to-major adverse kidney events (MAKE), time-to-next treatment, kidney response and safety. ResultsTotal 748 patients with RRMM utilizing pomalidomide were included; 440 had preserved kidney function, 210 had moderate CKD (eGFR 30-59 mL/min/1.73m2), and 98 had advanced CKD (eGFR < 30 mL/min/1.73m2). Mean age was 70.2 years, 43.3% were women. Patients with advanced CKD had a higher risk of all-cause mortality compared to the preserved kidney function group (aHR 1.37, 95% CI 1.06, 1.78). MAKE was higher in advanced CKD (aHR 1.70, 95% CI 1.03, 2.35). Kidney response was similar between moderate and severe CKD groups (aOR 1.04, 95%, CI 0.56-1.90). Safety outcomes were similar between groups. ConclusionsPatients with advanced CKD and RRMM on pomalidomide-based regimens exhibited reduced survival and a higher risk for MAKE. However, the probability of experiencing some degree of kidney recovery is 50% in both moderate and severe CKD, with comparable safety outcomes.

Health Care Access, Socioeconomic Status, and Acute Kidney Injury Outcomes: A Prospective National Study

Acute kidney injury (AKI) incidence and outcome in Kuwait are unknown. Moreover, non-Kuwaitis, who represent 66% of the population, have lower income, and their access to public health services is restricted compared with Kuwaitis who have free full access. Observational prospective multicenter cohort study. Adult inpatients with AKI in 7 public hospitals from January 1 to December 31,2021. AKI identified using Kidney Disease: Improving Global Outcomes serum creatinine-based criteria. For hospitalized patients with AKI, the outcomes included 30-day outcomes of mortality, need for dialysis, kidney recovery rates, and differences in outcomes between Kuwaitis and non-Kuwaitis. A backward stepwise multiple logistic regression analysis was performed to assess possible independent risk factors for the outcomes. We recruited 3,744 patients (mean age: 63 years; mean baseline estimated glomerular filtration rate [eGFR]: 66.7mL/min; non-Kuwaitis: 42.3%), representing 3.2% of hospitalizations and 19.5% of intensive care unit (ICU) admissions. Non-Kuwaitis were significantly younger (57.6 vs 66.9 years), with higher baseline eGFR (73.1 vs. 62mL/min), more frequent community acquired AKI (53.8% vs 46.7%), and AKI in summer (34.7% vs 26.9%). Dialysis was provided to 33.5% of patients, with a higher need for non-Kuwaitis (35.5% vs 32.1%). At 30 days, 34.4% of patients died, representing 24.8% of hospital mortality and 59.8% of ICU mortality. No differences in mortality or kidney recovery were noted between Kuwaitis and non-Kuwaitis. Low eGFR did not affect the mortality rate. Observational nature and short follow-up period of 30 days only. AKI was associated with high dialysis need and mortality. Non-Kuwaitis accounted for less cases despite representing 66% of the population because they were younger with higher baseline eGFR and fewer comorbid conditions. Non-Kuwaitis had higher rates of community acquired AKI and AKI in summer and a higher need for dialysis but had similar mortality and complete kidney recovery rates.

Acute kidney injury in children with lymphoma.

To analyze the epidemiology of acute kidney injury (AKI) in children with lymphoma and to assess the incidence, risk profile of AKI, and effects on renal function in children with lymphoma during their first 30 days of hospitalization. This was a retrospective screen of electronic hospital and laboratory databases to select hospitalized children who were first diagnosed and treated for lymphoma at Beijing Children's Hospital between 2020 and 2021. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. We analyzed the incidence and risk factors for AKI in children with lymphoma during their first 30 days of hospitalization. We also analyzed mortality rate and the incidence of kidney recovery over a 1-year follow-up period. Of the 295 children with lymphoma (which were all non-Hodgkin lymphoma), 42 (16.5%) experienced AKI events during the first their 30 days of hospitalization. The proportion of patients with lymphoma clinical stage 4 was higher in the AKI group than in the non-AKI group (66.7 vs. 43.7%, p<0.05). Tumor lysis syndrome (TLS), lung infection, and lymphoma clinical stage were identified as independent risk factors for AKI in children with lymphoma. Severe AKI was associated with TLS, sepsis, and a higher need for intensive care. Over 1-year of follow-up, none of the survivors developed impaired renal function or proteinuria. However, the mortality of children in the AKI group was significantly higher than that in the non-AKI group (p<0.05). TLS, lung infection, and lymphoma clinical stage were identified as independent risk factors for AKI in children with lymphoma during the first 30 days of hospitalization. Clinicians should increase their awareness of AKI in hospitalized patients with lymphoma.

A very complicated UTI: malakoplakia following E. coli urinary tract infection

Malakoplakia is a rare inflammatory disorder believed to result from a defect in macrophage phagocytic function triggering a granulomatous reaction. It can present with genitourinary, gastrointestinal, or cutaneous manifestations in immunocompromised or, less commonly, immunocompetent hosts. We describe a case of renal malakoplakia in a young, otherwise healthy patient presenting with nephromegaly and sepsis following an E. coli urinary tract infection. We discuss diagnosis and management, including antibiotic selection and the decision to pursue nephrectomy. This case highlights the potential for kidney recovery with prolonged antibiotic therapy in conjunction with adjunct immunomodulatory therapies and source control.

C3 Glomerulonephritis Associated with Monoclonal Gammopathy

C3 glomerulonephritis (C3GN) is rare. It is a proliferative glomerulonephritis resulting from glomerular deposition of complement factors due to dysregulation of the alternative pathway of complement. The association between monoclonal protein production and development of C3GN was described. We report a 74-year-old man with rapid worsening of kidney function and dialysis needed due to C3GN. In this case, serum protein electrophoresis showed no monoclonal spike but serum immunoelectrophoresis showed a lambda light chain monoclonal gammopathy. Once the diagnosis was made, the patient was treated with immunosuppression with complete kidney recovery. This case shows the importance of accurate and prompt diagnosis and appropriate treatment.

Clinicopathologic Characteristics of Crystalglobulin-Induced Nephropathy: A Case Series

Crystalglobulinemia is a rare syndrome characterized by intravascular crystallization of monoclonal immunoglobulins (MIgs). Data on kidney involvement are limited to case reports. This series characterizes the clinicopathologic spectrum of crystalglobulin-induced nephropathy (CIN). Case series. Nineteen CIN cases were identified from the nephropathology archives of Mayo Clinic and Columbia University. CIN was defined by intravascular (extracellular) MIg crystals visible by light (LM) and electron microscopy (EM). Among the cases, 68% were male and 65% were Caucasian (median age 56 years). Most patients presented with severe AKI (median creatinine 3.5 mg/dL), hematuria, and mild proteinuria (median 1.1 g). Common extrarenal manifestations were constitutional (67%), cutaneous (56%), and rheumatologic (50%). Fifty percent of cases had hypocomplementemia. The hematologic disorders were monoclonal gammopathy of renal significance (MGRS) (72%), lymphoma (17%), or myeloma (11%), with 65% of these disorders discovered concomitantly with CIN. All patients had MIg identified on SPEP/SIF (IgGκ in 65%). The sFLC ratio was outside the renal range in 40%, and bone marrow biopsy detected the responsible clone in 67%. On LM, crystals involved glomeruli (100%) and vessels (47%), often with an inflammatory reaction (89%) and fibrin (58%). All cases exhibited crystal substructures (mostly paracrystalline) by EM. Immunofluorescence (IF) on paraffin embedded tissue was more sensitive than frozen tissue (92% versus 47%) for demonstrating the crystal composition (IgGκ in 63%). Follow up (median 20 months) was available in 16 patients. Eighty-one percent received steroids, 44% plasmapheresis, 38% hemodialysis, and 69% chemotherapy. Ninety-percent of patients who received clone-directed therapy achieved kidney recovery vs. 20% of those who did not (p=0.017). Retrospective design, small sample size. CIN is a rare cause of nephropathy associated with lymphoplasmacytic disorders (mostly MGRS) and typically presents with severe AKI and extrarenal manifestations. Diagnosis often requires IF performed on paraffin embedded kidney tissue. Prompt initiation of clone-directed therapy, coupled with corticosteroids and plasmapheresis, may lead to recovery of kidney function.

Acute kidney injury after CAR-T cell therapy: exploring clinical patterns, management, and outcomes.

Acute kidney injury (AKI) has been reported after CAR-T cells, but available data are limited. We sought to describe the incidence of AKI in a cohort of patients hospitalized in the intensive care unit (ICU) following CAR-T cell reinjection, identify the primary factors linked to the onset of AKI, and ascertain the key determinants associated with kidney outcomes and mortality. We retrospectively analyzed 119 patients hospitalized in ICU after CAR-T cell therapy between 2017 and 2023. Factors associated with AKI, mortality, and kidney sequelae were identified using multivariate analyses. Of the 119 patients, 41 patients fulfilled diagnostic criteria of AKI (34%). By multivariate analysis, grade ≥3 cytokine release syndrome (CRS) [OR=1.20 CI95% (1.01-1.43)] and elevated lactate dehydrogenase (LDH) levels at admission [OR=1.44 CI95% (1.04-1.99)] were significantly associated with the occurrence of AKI during ICU stay. AKI KDIGO ≥2 was an independent risk factor for hospital mortality [OR=1.50 (1.22-1.85), P<0.001]. Nine out of 12 (75%) and 6/9 (67%) patients who had experienced AKI and survived had chronic kidney disease (CKD) at 6 months and 1 year, respectively. We did not identify any specific factor associated with kidney recovery. AKI may occur in ICU patients receiving CAR-T cell therapy, especially those who experience CRS and exhibit elevated LDH levels. Early recognition of AKI is of utmost importance as it substantially compromises survival in these patients. Future studies should aim to elucidate the underlying pathophysiological mechanisms of AKI in this context and pinpoint predictive factors for long-term risks of CKD.

#2262 Renal outcomes of postpartum atypical hemolytic uremic syndrome treated with plasma exchange

Abstract Background and Aims Postpartum acute kidney injury (AKI) with features of thrombotic microangiopathy (TMA) are particularly challenging and complex cases. Causes include Preeclampsia (PE), hemolysis, elevated liver enzymes and low platelet count syndrome (HELLP) and atypical hemolytic uremic syndrome (aHUS). In a limited resource setting, it is difficult to diagnose such cases with more than standard blood tests. Therapeutic Plasma exchange (TPE) is the only available option for treatment in the absence of complement inhibitors. This study evaluates renal outcomes in patients with aHUS treated with plasma exchange. Method This is a single centre observational study conducted in a Tertiary Obstetric Intensive Care unit. The data of women who were admitted with postpartum AKI from January 2021 to October 2023 was retrospectively collected and analyzed. We used the following criteria to diagnose postpartum atypical HUS (Serum creatinine ≥1.9 mg/dL, Lactate dehydrogenase (LDH) ≥1832 U/L, or serum creatinine ≥1.9 mg/dL in combination with LDH ≥600 U/L) [1]. Inclusion criteria include women older than 18 yrs with microangiopathic hemolytic anaemia, schistocytes on peripheral blood film, negative direct antiglobulin test (DAT) and platelet count &amp;lt;100 /mm3.Lack of improvement of kidney functions and hemolysis 72 hours after delivery. Patients with sepsis, disseminated intravascular coagulopathy (DIC), postpartum hemorrhage (PPH) and chronic kidney disease were excluded. We identified 10 patients with postpartum aHUS. Peak creatinine, LDH, AST and Nadir platelet count and hemoglobin were recorded. Patients were followed up in the nephrology outpatient clinic. Results Fifty-two patients developed postpartum AKI in the study period. Ten patients (19%) were diagnosed with aHUS according to the above-mentioned criteria. Mean age was 24.5 ± 6.9 yrs. Median peak creatinine 5.1 (2.6-7) mg/dl, LDH 1950 (612-4000) U/L, AST 246 (150-699) U/L. Median nadir hemoglobin 7.25 (6-8.2) g/dl and platelets 57 (41-95)/mm3. All 10 patients received 3 to 6 sessions of TPE guided by platelets and LDH levels. All patients required at least 3 sessions of hemodialysis. Eight patients received TPE with plasma filter and 2 had centrifugal TPE (due to lack of plasma filters). Two patients died during ICU admission. Two months after discharge 4 (50%) patients had partial recovery of kidney functions average creatinine (3.5 ± 0.8) mg/dl and four (50%) remained dialysis dependent. Six of these patients had kidney biopsies, three biopsies showed a picture of thrombotic microangiopathy and two showed thrombotic microangiopathy with renal cortical necrosis. The other patient was lost to follow up. Conclusion It is difficult to diagnose and treat aHUS in a resource limited setting. The available treatment with therapeutic plasma exchange has poor renal outcomes.

#1646 Impact of sex in clinical presentation and outcomes of patients with ANCA-associated vasculitis with severe kidney disease

Abstract Background and Aims Biological sex has been associated to a more rapid rate of chronic kidney disease progression (ie, speed of kidney function loss) in male than female [1]. Testosterone can increase oxidative stress, activate the renin angiotensin system, and aggravate renal fibrosis, whereas estrogens inhibit these pathological processes in the diseased kidney [2]. Several factors such as lower disease awareness and surveillance rates as well as disparities in health-care access result in late initiation or lack of kidney replacement therapy among females [3-5]. The impact of sex in the clinical presentation and outcomes of patients with anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) with glomerulonephritis (AAV-GN) has not been studied, particularly in patients with severe kidney involvement at presentation (eGFR&amp;lt;15 mL/min/1.73 m2). Method A retrospective cohort study on MPO- or PR3-ANCA positive patients with AAV (MPA or GPA) and eGFR&amp;lt;15 ml/min/1.73 m2 or ESKD at presentation. Clinical presentation and outcomes (renal recovery, dialysis at presentation, and ESKD) were analyzed according with sex. Results We analyzed 166 patients with biopsy proven active AAV-GN and eGFR &amp;lt;15 mL/min/1.73 m2 at the time of diagnosis (Fig. 1): 78 (47%) were females and 88 (53%) were males. Arterial hypertension was more frequently present in males (85.2% vs. 70.5%, p = 0.022). Median serum creatinine (SCr) was higher in males when compared with females (5.2 [IQR 4.2-7.4] vs. 3.6 [IQR 2.8-5.1] mg/dL, p &amp;lt; 0.001) but there were no differences in eGFR at presentation. When analyzing only the 71 (24 females and 47 males) patients that started dialysis within 4 weeks, infections at 12 months were more common in females (75.0% vs. 36.2%, p = 0.017). The rate of dialysis initiation or progression to ESKD was not different between males (15, 62.5%) versus females (29, 61.7%) being on dialysis at 12 months. By multivariable logistic regression, factors related with dialysis initiation within 4 weeks in our cohort were SCr (OR1.478, [95% CI 1.231-1.776], p &amp;lt; 0.001), alveolar hemorrhage (OR 2.726, [95% CI 1.099-6.763], p = 0.031) and PR3-ANCA (OR3.155, [95% CI 1.485-6.702], p = 0.003) adjusted to sex). Patients who remained on dialysis at 12 months more often had higher SCr at diagnosis (IRR 1.098 [95% CI, 1.026–1.175], p = 0.007), severe chronicity changes on kidney biopsies (IRR 2.469 [95% CI,1.205–5.061], p = 0.014), higher chronicity score (IRR 1.178 [95%CI, 1.062-1.308], p = 0.002) and lower hemoglobin (IRR 0.824 [95%CI, 0.683-0.994], p = 0.043). Minimal chronicity changes were protective for the achievement of this endpoint (IRR 0.228 [95% CI, 0.070-0.741], p = 0.014). Multivariable Cox regression showed that patients with higher SCr at diagnosis and moderate/severe chronicity changes on biopsy were at higher risk to evolve to ESKD at 12 months compared to patients with lower chronicity grades, even when adjusted to sex. Conclusion In our cohort, male patients presented with higher SCr, and dialysis was started within 4 weeks more frequently. However, this did not result in different outcomes in terms of kidney recovery, overall dialysis rates, and progression to ESKD in patients with AAV-GN and eGFR&amp;lt;15 mL/min/1.73 m2 between groups.

#1795 Diverse histological findings of kidney injury in cancer patients on immunotherapy- impact on clinical management

Abstract Background and Aims Immune checkpoint inhibitors (CPIs) are becoming rapidly more used to treat various types of cancer. Acute interstitial nephritis (AIN) is considered the most common pattern of kidney injury in these patients, however other distinct histological lesions are increasingly reported. The aim of this study is to assess the histological findings and the value of kidney biopsy in the management of patients with CPI-associated nephrotoxicity. Method All records from patients treated with CPIs and kidney injury that underwent a kidney biopsy during the last 4 years were retrospectively assessed. Results We included 16 biopsied patients treated with CPIs and kidney injury, 8 males and 8 females. The mean age at the time of renal biopsy was 68 (± 8.2) years and the median follow up time was 11.5 (8-29) months. The most common primary malignancy was non-small cell lung cancer (n = 8), followed by melanoma (n = 3), endometrial cancer (n = 2), renal cell carcinoma (n = 1), breast cancer (n = 1) and hepatocellular carcinoma (n = 1). At the time of kidney biopsy eleven patients were treated with pembrolizumab, three patients with ipilimumab and nivolumab combination, one patient with ipilimumab and one patient with atezolizumab. Eleven patients were on immune-chemo combined therapy. Twelve patients presented with acute kidney injury (AKI), two with nephrotic syndrome, one with nephrotic range proteinuria and one with acute onset of hypertension and subnephrotic proteinuria [Urine Protein (UPr): 3 g/24 h]. The median time to developing kidney injury from CPI initiation was 9 (4.25-21.5) months. The prevalent histologic lesion was AIN (n = 5), followed by three cases of mixed AIN with acute tubular injury (ATI), and two cases of pure ATI. We recorded three cases of CPI-associated glomerulonephritis including membranous nephropathy (MN) with a lupus-like pattern on immunofluorescence, AA amyloidosis and Focal Segmental Glomerulosclerosis (FSGS) cellular variant. Two patients had diabetic nephropathy (DN) with ATI and one patient had thrombotic microangiopathy (TMA) with ATI. Immunotherapy was temporarily withheld in all patients at the time of kidney biopsy. After the establishment of the histological diagnosis: we continued treatment with corticosteroids in nine patients (five cases with AIN, one case with mixed AIN/ATI, one case with MN, one case with FSGS and one case with TMA/ATI). Withdrawal of corticosteroids was decided in five cases (two patients with diabetic nephropathy, two patients with mixed ATI/AIN and one with ATI). The patient with AA amyloidosis was treated with colchicine and cortisone with partial remission of nephrotic syndrome (UPr: 1.2 g/24 h). In one case with pure ATI, corticosteroids, and the concomitant chemotherapeutic agent (pemetrexed) were withdrawn with complete response of AKI. Partial remission of proteinuria occurred in the patient with FSGS (UPr: 1.3 g/24 h). At the end of follow up, kidney recovery occurred in all 12 patients with AKI (among them one patient who required renal replacement therapy at the time of biopsy). Rechallenge with a CPI was attempted in 8 patients. After rechallenging, one patient experienced relapse of nephrotic syndrome (MN) and immunotherapy was withdrawn. The other seven patients continued CPI treatment without recurrence of kidney injury. The overall patient survival was 62.5%. Conclusion AIN is only one of the possible causes of nephrotoxicity in patients receiving CPIs. Kidney biopsy establishes the accurate diagnosis of CPI-associated AKI. In selected cases it allows the continuation of immunotherapy and can prevent the unnecessary use of corticosteroids.

#921 Interferon regulatory factor 4 (IRF4)-specific deletion on dendritic cells protects against kidney inflammation and injury in IRI-induced AKI/AKD

Abstract Background and Aims Ischemia-reperfusion injury (IRI) is a frequent clinical cause of acute kidney injury and disease (AKI/AKD) which can lead to acute tubular necrosis and irreversible kidney function loss. Mononuclear phagocytes, including dendritic cells (DCs), Monocytes, and macrophages, play important roles in various phases of injury and repair processes. Previous research has indicated that conventional dendritic cells (cDCs) are subdivided into cDC1s and cDC2s, and these two subsets could have opposing functions. We also demonstrated that cDC1s have a protective role as deficiency of cDC1s results in aggravated inflammation and injury in the IRI-induced AKI/AKD model in our previous study. Based on these researches, we aim to investigate the function of cDC2s in the IRI-induced AKI/AKD model. Method We used interferon regulatory factor 4 (IRF4)-deficient mice (IRF4fl/flClec9acre) to specifically delete IRF4 on DC lineage cells as our experimental group, and used wide-type mice as our control group. After unilateral IRI (UIRI) surgery, we measured the GFR and plasma creatinine of the mice on day 1 (D1) and day 5 (D5), then collected the injured kidney issue after sacrificing mice. We compared the differences between IRF4fl/flClec9acre mice and wild-type mice in terms of DC subpopulation changes, neutrophil accumulation, T cell differentiation, intensity of inflammatory responses, and tissue repair capabilities in damaged kidney tissue, by using techniques such as immunohistochemistry, immunofluorescence, flow cytometry, qRT-PCR, etc. Results ([KOMean-WTMean] ± SEM): IRF4fl/flClec9acre mice showed a lower percentage of cDC2s without affecting cDC1s in the kidney compared with wide-type mice (D1: −0.04467 ± 0.01356, P = 0.0301; D5: −1.108 ± 0.2248, P = 0.0004). During post-ischemic AKI/AKD, IRF4 deficiency in cDCs had several beneficial effects compared to wild-type mice, including reducing renal tubular cell injury (PAS score D1: −0.9375 ± 0.1523, P &amp;lt; 0.0001; PAS score D5: −1.119 ± 0.1445, P &amp;lt; 0.0001), decreasing loss of kidney function (GFR D1: 8.983 ± 4.091, P = 0.1041; GFR D5: 14.9 ± 5.01, P = 0.0172), and promoting kidney function recovery. This was associated with increased expression of anti-inflammatory cytokines (IL-4 D1: 4.486 ± 1.363, P = 0.0079; IL-4 D5: 3.403 ± 1.447, P = 0.0366; IL-10 D1: 2.103 ± 0.7342, P = 0.0299; IL-10 D5: 2.654 ± 0.8859, P = 0.0166), decreased expression of pro-inflammatory cytokines(TNF-α D1: −1.418 ± 0.5467, P = 0.0433; TNF-α D5: −2.434 ± 1.919, P = 0.0074; IL-23a D1: −1.320 ± 0.3432, P = 0.0061; IL-23a D5: −16.12 ± 3.587, P = 0.0004) and acute tubular cell death, reduced neutrophil chemoattractant expression (CXCL-2) (Fig. 6) and recruitment of neutrophils (−6.107 ± 1.664, P = 0.0214), and differentiation of Th2 (−0.1867 ± 0.03333, P = 0.005) and Th17 cells (−0.1767 ± 0.01333, P = 0.0002). Conclusion In conclusion, our data demonstrate a critical role of IRF4 in the kidney cDC2 subset and highlight that deficiency of cDC2s can protect against kidney inflammation, reduce kidney injury, and promote kidney recovery in the IRI-induced AKI/AKD model. This suggests that cDC2s have an immunoregulatory role in AKI/AKD and could serve as a potential therapeutic target for kidney inflammation.

#226 Outcome of intermittent hemodialysis vs. continuous kidney replacement therapy for acute kidney injury: observational prospective multi-center study

Abstract Background and Aims Continuous hemodialysis in hemodynamically stable acute kidney injury (AKI) patients may impact outcome differently compared to intermittent hemodialysis, although this issue is controversial. We look at differences in AKI outcomes between patients treated with intermittent hemodialysis (IHD) and patients treated with continuous kidney replacement therapy (CKRT) modalities in in Kuwait. Method Clinically and hemodynamically stable adult inpatients with native kidneys (i.e., did not need inotropic support or mechanical ventilation) who received IHD or CKRT for AKI, in seven public hospitals in Kuwait between 1/January to 31/December 2021 were recruited. CKRT was selected due to lack of access to water treatment in patients wards in some of the participating hospitals. Demographics, comorbidities, dialytic and non-dialytic management data, and 30-day kidney and patient outcome data for, were prospectively collected and analyzed. Results Total number of AKI patients not on inotropic support and not mechanically ventilated who received dialysis during study period was 229 (age: 59.9 years; males: 60.3%; baseline eGFR: 56 ml/min). IHD (group 1) was performed in 27.1% of the cohort whereas CKRT (group 2) was performed in 72.9%. There was no statistically significant difference between the two groups in age (58.4 for IHD and 59.9 for CKRT, p=0.6), baseline eGFR (55 ml/min for IHD and 56.4 for CKRT, p=0.8), sex ratio, incidence of diabetes, hypertension or cardiovascular disease, or cause of AKI. However, renin angiotensin aldosterone system inhibitors (RAASi) were precipitating factors for AKI more significantly in the IHD group (25.8% vs. 6% for CKRT, P ≤ 0.001). Intensive care unit (ICU) contributed 21% of cases (14.5% for IHD and 23.4% for CKRT, insignificant p value of 0.1). Also, there was no statistically significant difference in receiving intravenous fluids between the two groups (71% for IHD vs. 71.5% for CKRT, p=0.8), however, more patients in the IHD group received diuretics (62.9% vs 43.1% for CKRT, p=0.008). Dialysis vascular access was right internal jugular vein in 59% (75.8% FOR IHD vs. 52.7% for CKRT) followed by femoral vein in 35% of cases (19.4%). Extracorporeal membrane oxygenation (ECMO) was used in only two cases in the CKRT group. Of the total cohort, 21.8% died, with no difference between the two groups (16.1% for IHD vs 24% for CKRT, p=0.2). Partial recovery was higher in IHD group (30.8% vs.17.3%, p=0.046) and complete recovery higher in CKRT group 33.1% vs 13.5%, p=0.009). eGFR at 30 days was 53.2 ml/min with no statistically significant difference between the two groups (44.6 for IHD vs 56.1 for CKRT, p=0.15). Conclusion The IHD group and the CKRT group were statistically similar in basic characteristics and received similar lines of management, except for the diuretics. At 30 days, they had similar death rates but CKRT group had higher rates of complete recovery than the IHD group. This is in line with published literature that suggest CKRT may not improve mortality but may improve kidney recovery.

Surgical Aortic Valve Replacement and Renal Dysfunction: From Acute Kidney Injury to Chronic Disease.

Background: Surgical aortic valve replacement (SAVR) is often complicated by acute kidney injury (AKI). Identifying patients at risk of AKI is important to start nephroprotective strategies or renal replacement therapy (RRT). This study investigated the incidence and risk factors of post-operative AKI in SAVR patients. Chronic kidney disease (CKD) developed in the post-cardiac-surgery follow-up period was also assessed. Methods: A total of 462 SAVR patients were retrospectively enrolled. The primary endpoint was the occurrence rate of AKI after surgery. Kidney recovery, during two planned outpatient clinic nephrological visits within 12 months after the surgery, was assessed. Results: A total of 76 patients experienced an AKI event. A Kaplan-Meier analysis revealed that subjects with CKD stage IV had a time to progression of 2.7 days, compared to patients with stages I-II, who were characterized by the slowest progression time, >11.2 days. A Cox regression indicated that CKD stages predicted a higher risk of AKI independently of other variables. During their ICU stay, 23 patients died, representing 5% of the population, most of them requiring RRT during their ICU stay. A severe CKD before the surgery was closely related to perioperative mortality. During the follow-up period, 21 patients with AKI worsened their CKD stage. Conclusions: AKI represents a common complication for SAVR patients in the early post-operative period, prolonging their ICU stay, with negative effects on survival, especially if RRT was required. Pre-operative CKD >3 stage is an independent risk factor for AKI in patients undergoing SAVR.

Complement C3 Levels in Membranoproliferative and Post-infectious Glomerulonephritides

Objectives − Post infectious glomerulonephritis (PIGN) is the most common type of nephritis in children. Presentation is variable, and most cases initially have low serum complement C3. Membranoproliferative glomerulonephritis (MPGN) is a chronic nephritis less frequently seen in children and is also associated with low serum C3. While management of PIGN is predominantly supportive, MPGN usually requires immunosuppressive therapy. Differentiating PIGN from MPGN at presentation is difficult. Early diagnosis can help inform evaluation and treatment decisions.Materials and Methods − This is a retrospective study of all children 1-21 years of age diagnosed with PIGN and MPGN, treated by nephrologists at Nationwide Children’s Hospital between January 2014 and December 2019. Clinical data, results of kidney function, complement levels, urine testing and biopsy were collected. Children with other types of glomerulonephritis were excluded.Results − Fifty-seven children were included (43 with PIGN and 14 with MPGN). PIGN children were younger at presentation (median age: 7 vs 9.5 years, P=0.0159) and more likely to have a C3 level &lt;40 mg/dl compared to MPGN children (P=0.0031). Most children with PIGN (74.42%) had normal complement levels within 12 weeks after diagnosis compared to 35.71% of children with MPGN. More children with MPGN had evidence of chronic kidney disease as compared to PIGN children, who were more likely to have a full kidney recovery. Conclusions − Younger children with more significant hypocomplementemia at presentation were more likely to have PIGN than MPGN. We recommend earlier evaluation for MPGN in adolescents with milder degrees of hypocomplementemia (&gt;40 mg/dl).

A clinical score to predict recovery in end-stage kidney disease due to acute kidney injury.

Acute kidney injury (AKI) is a major contributor to end-stage kidney disease (ESKD). About one-third of patients with ESKD due to AKI recover kidney function. However, the inability to accurately predict recovery leads to improper triage of clinical monitoring and impacts the quality of care in ESKD. Using data from the United States Renal Data System from 2005 to 2014 (n=22922), we developed a clinical score to predict kidney recovery within 90 days and within 12 months after dialysis initiation in patients with ESKD due to AKI. Multivariable logistic regressions were used to examine the effect of various covariates on the primary outcome of kidney recovery to develop the scoring system. The resulting logistic parameter estimates were transformed into integer point totals by doubling and rounding the estimates. Internal validation was performed. Twenty-four percent and 34% of patients with ESKD due to AKI recovered kidney function within 90 days and 12 months, respectively. Factors contributing to points in the two scoring systems were similar but not identical, and included age, race/ethnicity, body mass index, congestive heart failure, cancer, amputation, functional status, hemoglobin and prior nephrology care. Three score categories of increasing recovery were formed: low score (0-6), medium score (7-9) and high score (10-12), which exhibited 90-day recovery rates of 12%, 26% and 57%. For the 12-month scores, the low, medium and high groups consisted of scores 0-5, 6-8 and 9-11, with 12-month recovery rates of 16%, 33% and 62%, respectively. The internal validation assessment showed no overfitting of the models. A clinical score derived from information available at incident dialysis predicts renal recovery at 90 days and 12 months in patients with presumed ESKD due to AKI. The score can help triage appropriate monitoring to facilitate recovery and begin planning long-term dialysis care for others.

A study of hospitalized COVID-19 patients with AKI in a setting of multiracial developing country

BackgroundThe commonest indication for hospitalization in COVID-19 patients is hypoxemia or severe respiratory symptoms. However, COVID-19 disease may result in extrapulmonary complications including kidney-related pathology. The reported incidence of renal involvement related to COVID infection varies based on geographical location.ObjectiveThis study aimed to assess the incidence rate of AKI in hospitalized COVID-19 patients and identify risk factors and prognostic predictors.MethodIn this retrospective study, we recruited hospitalized COVID-19 patients from January 2021 until June 2021 at the University Malaya Medical Center. The inclusion criteria were hospitalized for ≥ 48 h with confirmed COVID-19 infection and at least 18 years old. Patient demographic and clinical data were collected from electronic medical records. The staging of AKI was based on criteria as per KDIGO guidelines.ResultsOne thousand five hundred twenty-nine COVID patients fulfilled the inclusion criteria with a male-to-female ratio of 759 (49.6%) to 770 (50.3%). The median age was 55 (IQR: 36–66). 500 patients (32.7%) had diabetes, 621 (40.6%) had hypertension, and 5.6% (n = 85) had pre-existing chronic kidney disease (CKD). The incidence rate of AKI was 21.1% (n = 323). The percentage of COVID patients in different AKI stages of 1,2 and 3 were 16.3%, 2.1%, and 2.7%, respectively. Fifteen hospitalized patients (0.98%) required renal replacement therapy. 58.8% (n = 190) of AKI group had complete recovery of kidney function.Demographic factors included age (p < 0.001), diabetes (p < 0.001), hypertension (p < 0.012), CKD (p < 0.001), and vaccination status (p = 0.042) were associated with an increased risk of developing AKI. We found that the AKI cohort had statistically significant lower platelet counts and higher ferritin levels than the non-AKI cohort. AKI is a risk predictor of prolonged hospitalization (p < 0.001) and higher mortality rates (P < 0.001).ConclusionAKI is a common clinical complication among hospitalized COVID-19 patients. The etiology of AKI is multifactorial and may have an adverse impact on patient morbidity and mortality.