Evaluation of terlipressin-related patient outcomes in hepatorenal syndrome-acute kidney injury using point-of-care echocardiography.

BACKGROUND AND AIMS: Treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI), with terlipressin and albumin, provides survival benefits, but may be associated with cardiopulmonary complications. We analyzed the predictors of terlipressin response and mortality using point-of-care echocardiography (POC-Echo) and cardiac and renal biomarkers. APPROACH: Between December 2021 and January 2023, patients with HRS-AKI were assessed with POC-Echo and lung ultrasound within 6 hours of admission, at the time of starting terlipressin (48 h), and at 72 hours. Volume expansion was done with 20% albumin, followed by terlipressin infusion. Clinical data, POC-Echo data, and serum biomarkers were prospectively collected. Cirrhotic cardiomyopathy (CCM) was defined per 2020 criteria. RESULTS: One hundred and forty patients were enrolled (84% men, 59% alcohol-associated disease, mean MELD-Na 25±SD 5.6). A median daily dose of infused terlipressin was 4.3 (interquartile range: 3.9-4.6) mg/day; mean duration 6.4 ± SD 1.9 days; the complete response was in 62% and partial response in 11%. Overall mortality was 14% and 16% at 30 and 90 days, respectively. Cutoffs for prediction of terlipressin nonresponse were cardiac variables [ratio of early mitral inflow velocity and mitral annular early diastolic tissue doppler velocity > 12.5 (indicating increased left filling pressures, C-statistic: 0.774), tissue doppler mitral velocity < 7 cm/s (indicating impaired relaxation; C-statistic: 0.791), > 20.5% reduction in cardiac index at 72 hours (C-statistic: 0.885); p < 0.001] and pretreatment biomarkers (CysC > 2.2 mg/l, C-statistic: 0.640 and N-terminal proBNP > 350 pg/mL, C-statistic: 0.655; p <0.050). About 6% of all patients with HRS-AKI and 26% of patients with CCM had pulmonary edema. The presence of CCM (adjusted HR 1.9; CI: 1.8-4.5, p = 0.009) and terlipressin nonresponse (adjusted HR 5.2; CI: 2.2-12.2, p <0.001) were predictors of mortality independent of age, sex, obesity, DM-2, etiology, and baseline creatinine. CONCLUSIONS: CCM and reduction in cardiac index, reliably predict terlipressin nonresponse. CCM is independently associated with poor survival in HRS-AKI.

Intravenous BCAA Infusion Does Not Lead to a Sustained Recovery From Overt HE in ACLF - An Open Label Randomized Clinical Trial.

Background: Hepatic encephalopathy (HE) in acute-on-chronic liver failure (ACLF) is associated with significant morbidity and mortality. We conducted a prospective, randomized controlled clinical trial to study the efficacy of intravenous branched chain amino acids (IV-BCAA) with lactulose versus lactulose alone for improvement in HE at 24 h, day 3, and day 7. The primary outcome was an improvement in encephalopathy by ≥ 1 grade at 72 h. Patients and methods: European association for study of liver (EASL) defined ACLF patients with overt HE were assessed and randomized into the experimental arm (IV-BCAA - 500 mL/day for 3 days + Lactulose; n = 39) and the comparator arm (Lactulose alone; n = 37). Six patients developed COVID-19 after randomization and were excluded (4-experimental arm and 2-comparator arm). Results: Of 222 screened patients, 70 (35 in each arm) were included in the analysis. Baseline characteristics, including HE grade (2.9 ± 0.7 vs 2.8 ± 0.7; P = 0.86) and (chronic liver failure) CLIF-C ACLF score (54.2 ± 5.6 vs 54.8 ± 5.7; P = 0.65), were similar. Overall survival was 40% at 28 days (48.5% vs 31.4%; P = 0.14). Improvement in hepatic encephalopathy scoring algorithm (HESA) by ≥ 1 grade at 24 h occurred in 14 patients (40%) in the BCAA arm and 6 patients (17.1%) in the control group (P = 0.03) which translated to a shorter intensive care unit (ICU) stay. The median change in HESA at 24 h was greater in the BCAA arm than the control arm (P = 0.006), which was not sustained at days 3 or 7. Ammonia levels did not correlate with the grade of HE (Spearman's correlation coefficient (ρ) = - 0.0843; P = 0.29). Conclusion: Intravenous BCAA does not lead to a sustained improvement in HE grade in ACLF. Trial registration no: NCT04238416 (clinicaltrials.gov).

A Randomized Controlled Trial Comparing Remission Induction with Modified Multitarget Therapy with Intravenous Cyclophosphamide in Proliferative Lupus Nephritis.

Introduction: Therapy of proliferative lupus nephritis (PLN) is yet to be optimized. Standard of care for induction consists of intravenous (IV) cyclophosphamide (CYC) and steroids, which shows an improved outcome, but end-stage renal disease (ESRD) progression, increased mortality, and therapy-related adverse effects remain a major concern. The other treatment reported to induce early remission was the multitarget therapy comprising tacrolimus, mycophenolate, and steroid, but infections were high in the multitarget therapy. Considering azathioprine as a potentially safer and effective alternative anti-B-cell therapy, modified multitarget therapy (MMTT) was planned replacing mycophenolate with azathioprine. Material and Methods: A single-center, 24-week, open-label, randomized controlled trial comprising adults of age 18-65 years with biopsy-proven PLN was carried out. The intervention groups were 1) MMTT: tacrolimus 0.075 mg/kg/day and azathioprine 2 mg/kg/day and 2) IV CYC group with a starting dose of 0.75 (adjusted to 0.5-1.0) g/m2 every 4 weeks for 6 months. Both groups received 3 days of pulse methylprednisolone followed by a tapering course of oral prednisone therapy. Results: Among 100 randomized patients, 48 were in MMTT arm and 52 were in IV CYC arm. At the end of 24 weeks, overall remission (complete and partial) was comparable in both the arms: MMTT (86.36%) and IV CYC (87.75%). There was comparable proteinuria reduction and systemic lupus erythematosus disease activity index (SLEDAI) score improvement with recovery of complement level C3 in both groups. Major adverse events were numerically more in the IV CYC group, including one death from pneumonia. Conclusion: The MMTT arm is as effective as IV CYC in improving short-term outcome in PLN, with a comparable safety profile.

Radioiodine Therapy in Patient with Differentiated Thyroid Cancer and End-Stage Renal Disease on Maintenance Hemodialysis: Case Report with Review of Literature.

Surgical resection followed by radioactive iodine (131I) therapy constitutes a standard treatment for differentiated thyroid cancer. 131I is normally excreted through the kidneys, and treatment of patients with end-stage renal disease on hemodialysis requires special attention to the dose of 131I, the timing of dialysis, and radiation safety. We present a case of end-stage renal disease in a postthyroidectomy patient on hemodialysis who required radioactive iodine ablation, and we review the literature.

Serum catalytic iron and progression of chronic kidney disease: findings from the ICKD study.

BACKGROUND: The non-transferrin bound catalytic iron moiety catalyses production of toxic reactive oxygen species and is associated with adverse outcomes. We hypothesized that serum catalytic iron (SCI) is associated with progression of chronic kidney disease (CKD). METHODS: Baseline samples of the Indian Chronic Kidney Disease participants with at least one follow up visit were tested for total iron, iron binding capacity, transferrin saturation, SCI, ferritin and hepcidin. SCI was measured using the bleomycin-detectable iron assay that detects biologically active iron. Association with the incidence of major kidney endpoints, (MAKE, a composite of kidney death, kidney failure or > 40% loss of eGFR) was examined using Cox proportional hazards model adjusted for sex and age. RESULTS: 2002 subjects (49.9 ± 11.6 years, 68.1% males, baseline eGFR 41.01 ml/min/1.73m2) were enrolled. After a median follow up of 12.6 (12.2, 16.7) months, the composite MAKE occurred in 280 (14%). After adjusting for age and sex, increase from 25th to 75th percentile in SCI, transferrin saturation, ferritin and hepcidin were associated with 78% (43-122%), 34% (10-62%), 57% (24-100%) and 74% (35-124%) increase in hazard of MAKE, respectively. SCI was associated with MAKE and kidney failure after adjustment for occupational exposure, hypertension, diabetes, tobacco, alcohol use, history of AKI, baseline eGFR, uACR, and allowing baseline hazard to vary by centre. CONCLUSIONS: SCI is strongly and independently associated with composite MAKE in patients with mild to moderate CKD. Confirmation in other studies will allow consideration of SCI as a risk marker and treatment target.

Clinical Remission of Immunoglobulin A Nephropathy after Bariatric Surgery in a Young Morbidly Obese Patient.

A 23-year-old girl with morbid obesity, diabetes mellitus, hypertension, obstructive sleep apnea, and immunoglobulin A nephropathy (IgAN) attended a bariatric clinic after multiple failed attempts at weight loss. In the past, she was diagnosed with IgAN with nephrotic syndrome and raised blood pressure at the age of 11 years. Apart from optimization of blood pressure with angiotensin receptor blocker, she required steroid to maintain her remission in initial four years which was later switched to mycophenolate mofetil (MMF). She was diagnosed with diabetes at the age of 13 years; her blood sugars remained poorly controlled despite therapy with oral hypoglycemic agents and insulin. She underwent sleeve gastrectomy with no post-operative complications. During the follow-up, she showed a steady reduction in her weight, along with maintaining normal blood sugars and pressure without medications. At 18 months of follow-up, IgAN remained in remission after stopping MMF at four months after the surgery. Obesity is considered an important cofactor in the progression of IgAN. This case highlights the importance of weight reduction to halt the progression of the disease.

The changing face of pregnancy-related acute kidney injury from eastern part of India: A hospital-based, prospective, observational study.

This study was initiated to look into the etiologies, prevalence, and outcome of pregnancy-related acute kidney injury (PRAKI) in a tertiary care hospital. Women admitted with PRAKI from January 2015 to December 2016 were included in the study. All patients were investigated and treated and followed up for the next six months.. For statistical analysis, Chi- square test and analysis of variance were performed to analyze the data. Multivariate analysis was applied to compare the risk of nonrecovery of renal function in different etiologies of PRAKI. During the study period, 81 patients were admitted with PRAKI, of whom 68 (84%) received hemodialysis (HD). A total of 449 patients including all cases of AKI underwent HD from January 2015 to June 2016. The incidence of dialysis requiring PRAKI was 68 out of the 449 patients (15%). Sixty-eight (84%) patients required dialysis support while the most common cause was sepsis (49%), with the second being pregnancy-associated atypical hemolytic-uremic syndrome (P-aHUS) (17%) followed by obstetric hemorrhages (16%). There was a significant reduction of first-trimester AKI (8.6%) compared to a previous study published from this institute (19.3%). The maternal mortality (25%) and fetal mortality (23.5%) were high. Nearly 39% of the patients had complete recovery of renal function. This study revealed significant PRAKI burden due to a largely preventable cause, puerperal sepsis. Renal survival was poor in P- aHUS. The gaps in the obstetric care may be identified for the improvement of fetomaternal outcome.

Spectrum of renal allograft biopsy: A five-year experience at a tertiary care center of Eastern India.

Renal allograft dysfunction (RAD) can have myriad causes and presentations. Allograft biopsy remains the gold standard for optimum management. This is a retrospective study carried out at a tertiary care institute from August 2011 to March 2016. Details of the renal allograft biopsy requisitions were recorded and analyzed. Two hundred and two patients had undergone kidney transplantation (KT) during the study period. One hundred and twenty-six had undergone renal biopsy for RAD. The acute asymptomatic rise of serum creatinine was the most common clinical presentation (47.61%) followed by chronic RAD (CRAD) (19.84%), proteinuria (15.87%), immediate graft dysfunction (10.31%), and persistent active urinary sediments (6.34%) in that order. The incidence of delayed graft function was 1.98%. The overall incidence of biopsy-proven rejection was 8.41% within oneyear and 8.91% beyond oneyear of transplant. Acute cellular rejection (ACR) [with or without antibody-mediated rejection (AMR)] was found in 65%; AMR was found in 40% and 15% had both ACR and AMR. Borderline acute cell-mediated rejection was found in 22.5% of biopsies. CRAD was due to chronic rejection and chronic calcineurin inhibitor toxicity in only about one-fourth of the cases. Incidence of glomerulo-nephritis was 10.89% and most of these occurred two years after KT. Renal allograft biopsy was associated with minor complications in 3.17% of cases. Clinical presentations do not reliably distinguish the various causes of RAD. Allograft biopsy is a mainstay in the diagnosis of RAD and is safe. Results of live donor first transplantation using complement-dependent cytotoxi-city crossmatch are comparable to those programs using newer methods like solid-phase assays. However, the direct comparison of these results with other studies may not be completely applicable.