Use of synthetic adrenocorticotropic hormone in patients with IgA nephropathy

Abstract Background Synthetic adrenocorticotropic hormone (ACTH) has been demonstrated to be effective in patients with membranous nephropathy, minimal change disease and some histological subtypes of focal segmental glomerulosclerosis. Its clinical impact in patients with IgA nephropathy is currently unclear. Case presentation In this report, we describe the clinical use of ACTH in patients with IgA nephropathy. Three female patients (24–44 years) with overt proteinuria received intramuscular (IM) ACTH for varying time periods (8–14 months). Pre-treatment urine protein varied from 2.9 g/d to 4.3 g/d. Conclusions There was complete remission in one patient on ACTH monotherapy and in the other two when prescribed as a steroid-sparing agent in combination with cyclophosphamide. All three had resolution in proteinuria to less than 1 g/d and maintained their GFR to baseline values. There were no reported side effects at a once a week dose. This study illustrates that ACTH is an effective agent that is well tolerated with minimal side effects and can be used as an alternative to prednisone in patients with IgA nephropathy

Successful Use of Renal Denervation in Patients With Loin Pain Hematuria Syndrome—The Regina Loin Pain Hematuria Syndrome Study

Introduction: Loin pain hematuria syndrome (LPHS) is characterized by severe unilateral or bilateral loin pain that suggests a renal origin but occurs in the absence of identifiable or relevant urinary tract disease. Hematuria can either be microscopic or macroscopic, but the renal abnormalities responsible for the hematuria are unexplained. Debilitating pain refractory to conventional pain medications is the main cause of morbidity. Methods: We conducted a single-arm, single-center study. Twelve patients between the ages of 21 and 62 years (11 female, 1 male) with LPHS underwent endovascular ablation of the renal nerves between July 2015 and November 2016, using the Vessix renal denervation system. The primary objective was to achieve 30% reduction in self-reported pain with the McGill Pain Questionnaire (MPQ) at 6 months. The secondary objectives were to measure changes in disability (Oswestry Disability Index [ODI]), mood (Geriatric Depression Scale [GDS]), and quality of life (EuroQol-5D [EQ-5D] and the MOS 36-Item Short Form Survey [SF-36]) scores from baseline to 6 months postprocedure. Results: Ten of 12 patients at 3 months and 11 of 12 patients at 6 months reported a >30% reduction in pain based on the MPQ at 3 and 6 months. We found consistent improvements in MPQ, ODI, GDS, EQ-5D, and SF-36 scores from baseline to 6 months postprocedure. Conclusion: We conclude that renal denervation is associated with a considerable improvement in pain, disability, quality of life, and mood. Our results suggest that percutaneous catheter−based delivery of radiofrequency energy is a safe, rapid treatment option that should be considered in all patients with LPHS. Keywords: endovascular ablation of renal nerves, loin pain hematuria, pain relief, renal denervatio

A Bayesian reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial

Background Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework. Methods We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression. Results The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30%; 3.40%], − 0.39% [95% CrI − 3.46%; 3.00%], and 0.64% [95% CrI − 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38; − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66. Conclusions In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation

Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis.

ObjectivesAmong patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant.DesignSecondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722).SettingOne hundred-fifty-three ICUs in 13 countries.PatientsAltogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ).InterventionsNone.Measurements and main resultsTotal mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p p p p p p p p = 0.007).ConclusionsAmong STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions