Higher Prevalence of Concurrent Thrombocytopenia in Patients Receiving Continuous Renal Replacement Therapy in the Cardiac Intensive Care Unit.

INTRODUCTION: Thrombocytopenia (TCP) is a common finding in patients receiving continuous renal replacement therapy (CRRT). OBJECTIVE: The purpose of this study was to assess the nature of TCP in patients receiving CRRT. METHODS: This is a single-center case-control observational study of 795 patients involving over 166,950 h of delivered CRRT at Johns Hopkins Hospital. Concurrent TCP in patients receiving CRRT was defined as a decrease in platelet count of ≥50% any time within 72 h of initiation of CRRT with strict exclusion criteria. RESULTS: There was a higher incidence of TCP in the cardiac intensive care unit (CICU) (22.5%) compared to medical ICU (MICU) (13.1%). Using logistic regression, the odds of developing concurrent TCP in patients receiving CRRT was 2.46 (95% CI 1.32-3.57, p < 0.05) times higher in the CICU compared with the MICU. There was no difference in the incidence of severe or profound TCP or timing of acute TCP between the CICU and MICU. CONCLUSION: Safe delivery of dialysis care in the ICU is paramount and creating awareness of potential risks such as concurrent TCP in patients receiving CRRT should be part of this care.

A review of the utility of tacrolimus in the management of adults with autoimmune hepatitis.

BACKGROUND: There is paucity of data on alternative drug therapies for patients with autoimmune hepatitis (AIH). Tacrolimus (TAC) is a promising salvage agent. We present a review of TAC therapy in AIH patients. METHODS: A search for studies with keywords 'autoimmune hepatitis' and 'tacrolimus' was performed. Reviews, studies of AIH post-transplant and AIH in children were excluded. Diagnosis of AIH was based on criteria established by the International Autoimmune Hepatitis Group. Complete biochemical response was defined as normalisation of aspartate aminotransferase (AST <45) and alanine aminotransferase (ALT <50). No biochemical response was defined as failure to return to normalisation at the end of follow-up. Demographic information and details of pre- and post-treatment liver biopsy were collected. RESULTS: Seven articles achieved the inclusion criteria and reported data for a total of 162 adult patients. The majority of studies reported average ages approximately 35 years old. Treatment duration ranged from 1 to 136 months. Indications for therapy were mostly AIH refractory to steroid treatment or inability to tolerate standard steroid treatment. Eighty-three patients (51.2%) were reported to have pre-therapy liver biopsy. Of 49 patients for whom stage was reported, 6 patients were stage 1, 16 were stage 2, 14 were stage 3 and 13 were stage 4. Of 40 patients for whom grade was reported, 1 patient was grade 0, 3 were grade 1, 9 were grade 2, 14 were grade 3 and 13 were grade 4. Dosing regimens were between 1 and 8 mg/day. Target trough TAC serum concentrations ranged from 0.5 to 10.7 ng/mL TAC was discontinued in 28 (17.3%) patients for various reasons. Renal function remained stable in most patients. One hundred and twenty-one patients (74.7%) demonstrated complete biochemical response to treatment. Post-therapy liver biopsy was obtained for 30 (18.5%) patients, and 25 (15.4%) of these patients were noted to have histological remission according to the grade of inflammation or stage of fibrosis. CONCLUSION: TAC is relatively effective in the treatment of AIH refractory to traditional therapy. It appears that liver function can be enhanced at a minimal cost to renal function. Key Points There is a cohort of patients with autoimmune hepatitis (AIH) who do not respond to standard therapy. Alternative treatment options for these patients have been explored, but outcomes have not been comprehensively examined. We report the use and efficacy of tacrolimus (TAC) in patients with AIH. We found that TAC can be safely and effectively used in patients with AIH with minimal side effects. TAC can be a potential treatment option for patients with AIH refractory to standard therapy.

Low-Level Proteinuria in Systemic Lupus Erythematosus.

INTRODUCTION: In patients with systemic lupus erythematosus (SLE) without concurrent active urinary sediment or unexplained acute kidney injury (AKI), current guidelines recommend performing a kidney biopsy in those with at least 500 mg/24-hour (European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association [EULAR/ERA-EDTA]) or 1000 mg/24-hour (American College of Rheumatology [ACR]) proteinuria. To evaluate the relevance of these indications, we studied histopathologic findings in patients with SLE with proteinuria below these cutoffs. METHODS: We retrospectively reviewed the clinical, laboratory and histological characteristics of patients with SLE with <1000 mg/24-hour proteinuria (or mg/g urinary protein-to-creatinine ratio [UPCR]) who underwent their first kidney biopsy between 2003 and 2018. RESULTS: We identified 87 patients with SLE with proteinuria less than 1000 mg/24-hour (or mg/g UPCR); 52 of 87 (60%) with isolated proteinuria, that is, without AKI or active urinary sediment (hematuria). Histologic evidence of lupus nephritis (LN) was present in 40 of 52 (76%). Of the 40 patients with LN, 12 had class I or II, 14 had class III or IV, 8 had class V, 6 had a combined proliferative and membranous LN. Non-lupus diagnoses included focal segmental glomerulosclerosis, acute interstitial nephritis, and others. Patient's age, low C3, low C4, and positivity for anti-double-stranded DNA (anti-dsDNA) antibodies predicted the histological diagnosis of LN on univariate logistic regression; however, a multivariate model including these parameters as independent covariates failed to predict LN. CONCLUSIONS: Patients with SLE with low-level proteinuria may have significant lupus- or non-lupus-related kidney disease with management implications. There was a significant burden of severe forms of LN. The presence of LN was not predicted by laboratory abnormalities. Based on our findings, we suggest current guidelines be revised to expand kidney biopsy indications to include isolated proteinuria of any grade.

Association of HIV Suppression With Kidney Disease Progression Among HIV-Positive African Americans With Biopsy-Proven Classic FSGS.

BACKGROUND: In the era of combined antiretroviral therapy, classic focal segmental glomerulosclerosis (FSGS) is the most common histopathological finding in African American HIV-positive patients with kidney disease. We sought to determine whether HIV suppression is associated with lower risk of progression to end-stage renal disease (ESRD) among HIV-positive African Americans with biopsy-confirmed classic FSGS. METHODS: HIV-positive African Americans who underwent kidney biopsies at a single tertiary hospital between January 1996 and June 2011 were confirmed as having classic FSGS by the presence of segmental glomerulosclerosis without features of HIV-associated nephropathy. Multivariable Cox proportional hazards models were used to examine the independent association of viral suppression (HIV-RNA < 400 copies per milliliter at biopsy) with time to progression to ESRD. RESULTS: Of the 55 HIV-positive African Americans with classic FSGS, 26 had suppressed viral loads at the time of biopsy. Compared to viremic patients, those who were virally suppressed had a significantly higher mean CD4 cell count (452 vs. 260 cell/mm, respectively; P = 0.02) and median estimated glomerular filtration rate (53.5 vs 35.5 mL/min/1.73 m, respectively; P = 0.002). Adjusting for sex and baseline CD4 cell count, estimated glomerular filtration rate, and proteinuria, those with HIV-RNA levels <400 copies per milliliter at baseline had a 75% lower risk of progressing to ESRD (hazard ratio = 0.25; 95% CI: 0.07 to 0.88) during a median follow-up time of 2.70 years (interquartile range: 0.80-5.15 years). CONCLUSIONS: HIV suppression is associated with significantly lower risk of progression to ESRD among HIV-infected African Americans with classic FSGS, supporting the potential role of combined antiretroviral therapy for this histopathology in addition to HIV-associated nephropathy among HIV-positive individuals.