Evaluating the Potential Role of Corticosteroids in Post-Infectious Glomerulonephritis

Acute poststaphylococcal glomerulonephritis superimposed on diabetic glomerulosclerosis

Changes in BMI Are Associated with Higher Distant Failure and Lower Overall Survival in Patients with Advanced Breast Cancer

Acute Poststreptococcal Glomerulonephritis: The Most Common Acute Glomerulonephritis

Bacterial infection-related GN occurs concurrent to or after known or unknown infections. It is important to understand the clinical implications of the bacterial isolates, antimicrobial resistance patterns, and effect of latency-based classification on kidney and patient outcomes. In total, 501 consecutive adults diagnosed with bacterial infection-related GN between 2005 and 2017 were included from a biopsy registry of 15,545 patients at a single center in South India, and follow-up data were collected from electronic medical records until December 2019. Latency was defined as time between resolution of infection and onset of GN, which was classified as parainfectious, peri-infectious, or postinfectious GN. Longitudinal kidney and patient outcomes were studied. The mean age of the cohort was 40 (± 15) years, 6% were above 65 years, and 330 (66%) were men. Diabetes was present in 93 (19%) patients. Seventy percent (353 of 501) of patients had known infections, with the median latent period for parainfectious (115 of 353, 33%), peri-infectious (97 of 353, 27%), and postinfectious (141 of 353, 40%) GN being 0, 5 (4-7), and 15 (10-31) days, respectively. The most common predisposing organism was Streptococcus pyogenes (137 of 353, 39%). Drug-resistant nonstreptococcal bacteria were methicillin-resistant Staphylococcus aureus (25%, four of 16), extended-spectrum β-lactamases (20%, 12 of 59), and carbapenem-resistant organisms (10%, six of 59). Twenty of 22 (91%) of the drug-resistant organisms were isolated from the parainfectious group. The most common site of infection was skin in peri- (23 of 97, 24%) and postinfectious GN (61 of 141, 43%), and urinary tract in parainfectious GN (35 of 115, 30%). Of 321 patients with >3 months of follow-up, 48 (15%) developed kidney failure over a median period of 10 (2-37) months and 14 (4%) died. Parainfectious GN, eGFR<30 ml/min per 1.73 m2, moderate-to-severe interstitial fibrosis and tubular atrophy, and nontreatment with renin-angiotensin system blockers were significant risk factors for progression to kidney failure by a Cox proportional-hazards model. Along with clinical and histologic predictors, parainfectious GN caused predominantly by nonstreptococcal and drug-resistant bacterial infections was associated with poor kidney prognosis.

We report the case of an adult who developed severe post-streptococcal reactive arthritis (PSRA) and poststreptococcal glomerulonephritis (PSGN) after a subclinical streptococcal infection. Antistreptococcal antibody titres, renal biopsy and the clinical course confirmed the diagnosis. Coincidence of PSRA and PSGN is rare in the adult population and the potential for misdiagnosis exists, particularly when prior streptococcal infection is not apparent. The clinical manifestations of poststreptococcal syndromes are highly variable, and the diagnosis of concomitant PSRA and PSGN should be considered when patients present with glomerulonephritis and inflammatory arthritis. Factors from both the host and the pathogen are probably important in determining disease expression in poststreptococcal syndromes.

Background: Post streptococcal glomerulonephritis with crescentic glomerulonephritis is an uncommon outcome in children. This study was done to evaluate the clinical spectrum and outcome in children with crescentic glomerulonephritis following acute post-streptococal glomerulonephritis. The diagnosis of underlying renal disease was based on various criteria, including the clinical picture, serology and histopathology. The patients received treatment in the form of intravenous methyl prednisolone, oral steroid treatment, and oral cyclophosphamide .Objective: to evaluate the clinical spectrum and outcome of the pediatric patients with post-streptococal crescentic glomerulonephritis admitted or referred in Zagazig general hospital in nephrology unit. Study design: The study included ( 20 ) children patients with biopsy proven crescentic golmerulonephritis following APSGN admitted or referred from other hospitals to the nephrology unit in Zagazig general hospital between Marsh 2010 to May 2016 These patients were subjected to detailed clinical and biochemical examinations including urine analysis ,U&amp;E ,serum albumin, ASOT ,anti- DNase-B test, complements ( C3 and C4), ANA, ANCAs ,anti- DNA antibodies; anti-(GBM) antibodies . The diagnosis of underlying renal disease was based on various criteria, including the clinical picture, serology and histopathology by light immunofluorescence and electron microscopy and all patients were taken immunosuppressive treatment.Results: 20 patients with poststreptococcal crescentic glomerulonephritis (12 males and 8 females). The mean age of patients at the time of presentation was (7.5) years with range of 5 to 12 years. All were having gross hematuria ,progressive rise of serum creatinine, mean creatinine was 571.5 umol/l with range of (413umol/- 822umol/1) ,low complement C3, 16 patients were having hypertension (80%),10 patients (50%) had nephrotic range of proteinuria and remaining were having moderate range. Renal biopsy which revealed more than 50% crescents in all biopsies with mean of 62.5% and ranging between 50-90%. 4 patients had fibrocellular crescents (20%) and 16 had cellular crescents (80%). the mean follow up duration in months was 25 mo ranging between 22-28 months after immunosuppression,16 patients regained their normal kidney functions (80%) with mean creatinine 47 umol/l ranging between (40-68) P-value &lt;0.001**.4 patients (20%) had residual renal impairment, these 4 patients had fibro cellular crescents in renal biopsy. 8 patients regained their normal blood pressure at last follow up (80%) P-value &lt;0.001**.Conclusion: the overall outcome of 20 patients with post streptococcal crescentic glomerulonephritis was accepted &amp; excellent, 16 patients out of 20 (80%) regained their normal kidney functions. Due to the limited number of our patients , large multi-center study is needed to prove this result.

Retrospective studies suggest that immunosuppressive treatment of immune-related adverse events (irAEs) impairs survival in patients with melanoma who received immune checkpoint inhibitors. Here, we study this association across tumor types using data from six international phase II/III registrational trials. A post hoc analysis was performed on individual patient data from the anti-programmed cell death-1 (anti-PD-1) + anti-cytotoxic T lymphocyte-associated protein-4 (anti-CTLA-4) treatment arms of six clinical trials (CheckMate-067, -142, -214, -648, -743, and -9LA). Among patients who received systemic immunosuppression for treatment-related adverse events (trAEs), associations of peak and cumulative corticosteroid dose, and use of second-line immunosuppression with overall survival (OS) and progression-free survival (PFS) were assessed using multilevel Cox regression with adjustment for age and sex. Of the 1,959 patients who received anti-PD-1 + anti-CTLA-4 therapy, 834 patients who were treated with immunosuppression for trAEs were included. Eight hundred and thirty-two patients (100%) received corticosteroids and 81 patients (10%) received second-line immunosuppressants. High corticosteroid peak dose was associated with worse PFS: adjusted hazard ratio (HRadj), 1.15 (95% CI, 1.02 to 1.29) for 1 versus 0.5 mg/kg prednisolone and HRadj, 1.43 (95% CI, 1.05 to 1.96) for 2 versus 0.5 mg/kg. Similar effects were observed for OS: HRadj, 1.21 (95% CI, 1.06 to 1.39) and HRadj, 1.66 (95% CI, 1.17 to 2.37) for 1 and 2 versus 0.5 mg/kg, respectively. Cumulative corticosteroid dose was not associated with survival. HRadj of use of second-line immunosuppression was 1.23 (95% CI, 0.90 to 1.68) for PFS and 1.25 (95% CI, 0.88 to 1.77) for OS. Higher corticosteroid peak dose for trAEs is associated with worse survival across tumor types, while cumulative dose is not. Too few patients received second-line immunosuppressants to confirm or reject an association with survival. These data argue for a reconsideration of irAE management approaches, starting with lower corticosteroid dose whenever feasible.

To determine the effect of intra-articular corticosteroid injections on lumbar spine trabecular density. This retrospective study was IRB-approved and HIPAA-compliant. We identified 50 patients (26F, 24M, mean age 69 ± 14years) who had undergone at least three medium or large joint corticosteroid injections using insoluble corticosteroids and a subsequent non-contrast abdominal CT within 5years of the first injection. About 126 age- and sex-matched controls without history of prior corticosteroid use who had undergone non-contrast abdominal CT were identified. Cumulative corticosteroid dose was calculated. Density measurements (HU) of trabecular bone of L1 to L4 were performed, and measurements of L1 were compared to established normative data. Groups were compared using a two-sided paired t-test or a chi-squared test. Linear regression analysis between cumulative corticosteroid dose and trabecular density was performed. Patients underwent a mean of 4 corticosteroid injections (range 3 to 11) with a mean cumulative corticosteroid dose of 232 ± 100mg triamcinolone equivalent (range 120mg to 480mg). There was no significant difference in trabecular density of L1 to L4 between cases and controls, and there was no significant difference in trabecular density at L1 compared to normative data (p > 0.2). There was no association between cumulative intra-articular corticosteroid dose and mean lumbar trabecular density (p > 0.3). Patients who underwent repetitive intra-articular insoluble corticosteroid injections showed no increased risk of bone loss compared to controls. Cumulative intra-articular corticosteroid dose was not associated with lumbar trabecular density.

Systemic postnatal corticosteroids are used to treat or prevent bronchopulmonary dysplasia (BPD) in extremely preterm (EP) or extremely low birth weight (ELBW) infants but are associated with long-term harm. We aimed to assess the relationship between cumulative postnatal corticosteroid dose and neurodevelopmental outcomes. Longitudinal cohort study of all EP/ELBW livebirths in Victoria, Australia 2016-2017. Perinatal data were collected prospectively. Neurodevelopmental assessment was performed at 2 years' corrected age. Linear and logistic regression were used to determine relationships between cumulative corticosteroid dose and neurodevelopment, adjusted for gestational age, birth weight, sex and major intraventricular haemorrhage. Seventy-six EP/ELBW infants received postnatal corticosteroids to treat or prevent BPD, 62/65 survivors were seen at 2 years. Median (IQR) cumulative postnatal corticosteroid dose was 1.36 (0.92-3.45) mg/kg dexamethasone equivalent. Higher cumulative corticosteroid dose was associated with increased odds of cerebral palsy, adjusted OR (95% CI) 1.47 (1.04, 2.07). Higher cumulative corticosteroid dose was also associated with lower cognitive and motor developmental scores, however, this weakened after adjustment for confounding variables: cognitive composite score adjusted coefficient (95% CI) -1.3 (-2.7, 0.1) and motor composite score adjusted coefficient (95% CI) -1.3 (-2.8, 0.2). Higher cumulative postnatal corticosteroid dose in EP/ELBW infants is associated with increased odds of cerebral palsy at 2 years' corrected age. Adequately powered studies are needed to assess the independent effects of cumulative steroid dose on neurodevelopmental outcomes.

183 Background: Recent studies have reported that methadone has antineoplastic activity. Other studies have associated methadone with lower overall survival in patients with chronic pain. Methadone is the most frequent opioid chosen for purpose of opioid rotation (OR) in cancer patients experiencing refractory pain or opioid induced neurotoxicity. There is no data available on the association of methadone with overall survival in cancer patients. Our aim was to compare the characteristics and overall survival in cancer patients in methadone group with other strong opioid group. Methods: In this ad hoc analysis, we reviewed 2471 consecutive patient visits to the supportive care center of a tertiary cancer center in 2008 for ORs from strong opioids to methadone or other strong opioids with a follow-up visit within 6 weeks. Information regarding demographics, Edmonton Symptom Assessment Scale (ESAS), and morphine equivalent daily dose (MEDD) were collected. Successful pain response was defined as 2-point or 30% reduction in pain score. Kaplan-Meier curves were used to evaluate survival. Results: Of the 102 eligible patients, 54 underwent OR to methadone and 48 to other strong opioids. The median age was 56 years, 56% were male, and 81% had advanced cancer. There were no significant differences between the methadone group and the other opioid group in patient characteristics, performance status, MEDD, and ESAS scores. Although both the groups showed significant pain response, methadone group (72%) had a significantly higher pain response as compared to the other opioid group (65%; P = 0.04). The Kaplan-Meier curves revealed no significant difference in overall survival (OS) between the methadone group and the other opioid group [median OS: 5.2 months (95% CI 3.64-7.41) vs. 5.9 months (95% CI 2.6-9.2); P = 0.89]. Conclusions: We observed no significant difference in overall survival in cancer patients in methadone group as compared to other opioids. Further validation studies in a larger sample are warranted.

Streptococcal pyrogenic exotoxin B antibodies in a mouse model of glomerulonephritis

Controversy concerns immunological and ultrastructural features of acute poststreptococcal glomerulonephritis. Opportunity to study, by renal biopsy, immunohistochemistry and electron microscopy, an entire single population of patients with poststreptococcal glomerulonephritis permitted us to resolve several conflicts and to learn more of pathogenesis and natural history. An epidemic of 26 cases of acute poststreptococcal glomerulonephritis occurred among Red Lake Reservation Indian children 2 to 15 years of age. Type 49 beta hemolytic streptococci reappeared at Red Lake for the first time since the 1953 epidemic of acute glomerulonephritis. Clinical manifestations were minimal but most children had pustular streptococcal skin lesions. Endothelial proliferation and leukocytic infiltration was observed in percutaneous renal biopsies. As regularly observed in our previous studies of sporadic acute glomerulonephritis, approximately ¼ of these patients had nodular deposits of IgG and beta 1C globulin along the glomerular basement membranes by immunohistochemical analysis. 90 % of remaining patients showed interrupted linear deposition of beta 1C along glomerular membranes without IgG. Electron microscopic study revealed minimal development of the characteristic discrete electron dense deposits' on the epithelial side of the glomerular basement membrane. Focal membrane thickening and basement membrane-like material among mesangial cells was observed. This study, sampling an entire spectrum of acute poststreptococcal glomerulonephritis, suggests that nephritogenic strains of streptococci may exert a toxic action rendering the glomerulus susceptible to injury by antigen-antibody complexes. (Supported by American Heart Association, USPHS, and Minn. Heart) (SPR)

1. Hannah S. Kim, MD* 2. Francesca Costigliolo, MD† 3. Serena Bagnasco, MD† 4. Jeffrey Fadrowski, MD, MHS* 5. Rebecca L. Ruebner, MD, MSCE* 1. *Division of Pediatric Nephrology and 2. †Division of Pathology, Johns Hopkins University, Baltimore, MD A 5-year-old former 34-week girl with trisomy 21, hypothyroidism, and obstructive sleep apnea presents to the emergency department with a chief complaint of fever. She initially presented to her pediatrician 3 weeks earlier with sore throat and was diagnosed as having group A streptococcal pharyngitis. She completed 10 days of amoxicillin with resolution of sore throat. Now for the past 3 days she has had fever, chest pain, decreased enteral intake, and emesis. Review of systems is negative for diarrhea, gross hematuria, dysuria, polyuria, polydipsia, edema, weight loss, rash, arthralgia, arthritis, oral ulcers, epistaxis, and hemoptysis. She has had normal growth. She takes levothyroxine and took several doses of ibuprofen for fever over the past several weeks. There is no family history of kidney disease. She had no recent travel or sick contacts. On physical examination her weight is 45.2 lb (20.5 kg) (65th percentile); height, 46.1 in (117 cm) (62% percentile); temperature, 100.8°F (38.2°C); heart rate, 110 beats/min; respiratory rate, 24 breaths/min; oxygen saturation, 100% on room air; and blood pressure, 92/42 mm Hg (systolic 31st and diastolic 9th percentiles for age and sex). There is no pharyngeal injection or exudate. She appears well-hydrated, including moist mucous membranes. Lungs are clear to auscultation. Her abdomen is soft, nontender, and nondistended. There is no edema, and she has brisk capillary refill. She has no rash or joint swelling, erythema, or warmth. Laboratory evaluation includes a white blood cell count of 15,310/µL (15.31×109/L) with 83.6% neutrophils and 0.8% bands; hemoglobin …

Background: Glomerulonephritis (GN) is a rare kidney disease that causes significant morbidity and mortality. They are frequently difficult to treat, and in some cases, no treatment is available, and they can progress to chronic kidney disease (CKD) and end stage renal disease (ESKD). Kidney biopsy is the preferred diagnostic method because it helps determine the precise specific diagnosis, assesses the level of disease activity and severity, and thus aids in proper therapy and prognosis prediction. Methods: Retrospective review of 40 children under the age of 15 with GN diagnosed between 2019 and 2022. Nephrotic syndrome, sub-nephrotic proteinuria, nephrotic syndrome (NS) with acute kidney injury (AKI), subnephrotic proteinuria plus AKI, isolated hematuria, and unexplained renal impairment were the six clinical syndromes for which a kidney biopsy was performed in 25 patients. Hospital admission records, progression notes, and outpatient follow up were used to collect data. Results: Acute glomerulonephritis (AGN) with nephritic syndrome (NS) affected 53% of the patients. Patients with AGN-NS were more likely to develop hypertension (48.0% vs. 15.7%) and acute renal damage (32% vs. 10%). 48% of the patients had Acute Postinfectious Glomerulonephritis. 5% of the patients had membranoproliferative glomerulonephritis. 2.5% of patients with ANCA-negative rapidly progressive glomerulonephritis had extramembranous glomerulonephritis, and 2.5% had extracapillary glomerulonephritis. The kidneys of 24 people were biopsied. The most common reason for a kidney biopsy was rapidly progressing glomerulonephritis. Conclusion: Acute postinfectious glomerulonephritis has been the most common glomerulonephritis in our study over the last three years in our Marrakech department. It manifested as a rapidly progressive glomerulonephritis in twelve of the cases.

Meld Scoring System to Predict Outcomes in Patients Who Undergo VV ECMO Implantation