How I Approach Light Chain Amyloidosis.

Immunoglobulin Light Chain Amyloidosis (AL) is a progressive disease which leads to organ dysfunction and death. Tremendous progress has been made in staging, response, and treatment. The key to better survival though is early diagnosis which can be difficult since the symptoms are often nonspecific and can be seen in more common conditions. Once the diagnosis is confirmed, staging systems are available to provide prognosis on overall and renal survival. There are a number of treatments now available that are effective and well-tolerated. Response criteria have also been developed for hematologic and renal response in order to maximize response and minimize adverse effects. Newer therapies are being developed in particular anti-fibril therapies that are in clinical trials. For those patients who had a very good partial response or better, kidney transplantation may be an option if the kidney failure is not reversed.

Spurious Electrolyte and Acid-Base Disorders in the Patient With Cancer: A Review.

Electrolyte and acid-base disorders are frequently encountered in patients with malignancy, either due to cancer itself or as a complication of its therapy. However, spurious electrolyte disorders can complicate the interpretation and management of these patients. Several electrolytes can be artifactually increased or decreased such that the serum electrolyte values do not correspond to their actual systemic levels, potentially resulting in extensive diagnostic investigations and therapeutic interventions. Examples of spurious derangements include pseudohyponatremia, pseudohypokalemia, pseudohyperkalemia, pseudohypophosphatemia, pseudohyperphosphatemia, and artifactual acid-base abnormalities. Correctly interpreting these artifactual laboratory abnormalities is imperative for avoiding unnecessary and potentially harmful interventions in cancer patients. The factors influencing these spurious results also must be recognized, along with the steps to minimize them. We present a narrative review of commonly reported pseudo electrolyte disorders and describe strategies to exclude erroneous interpretations of these laboratory values and avoid pitfalls. Awareness and recognition of spurious electrolyte and acid-base disorders can prevent unnecessary and harmful treatments.

Transitional B cell cytokines risk stratify early borderline rejection after renal transplantation.

Borderline rejection (BL) in renal transplantation is associated with decreased allograft survival, yet many patients with BL maintain stable graft function. Identifying patients with early BL at risk for shortened allograft survival would allow for timely targeted therapeutic intervention aimed at improving outcomes. 851/1187 patients transplanted between 2013-18 underwent early biopsy (0-4 mos). 217/851 (25%) had BL and were compared to 387/851 without significant inflammation (NI). Serial surveillance and for-cause biopsies and seven-year follow-up were used to evaluate histological and clinical progression. To identify high-risk patients, we examined clinical/histological parameters using regression and non-linear dimensionality reduction (tSNE) and a biomarker based on peripheral blood transitional-1 B cell (T1B) IL-10/TNFα ratio. Compared to NI, early BL was associated with increased progression to late acute rejection (AR; 5-12 mos), premature interstitial fibrosis and tubular atrophy (IFTA) and decreased seven-year graft survival. However, decreased graft survival was limited to BL patients who progressed to late AR or IFTA, and was not influenced by treatment. Although tSNE clustered patients into groups based on clinical factors, the ability of these factors to risk stratify BL patients was modest. In contrast, a low T1B IL-10/TNFα ratio at 3 months identified BL patients at high risk for progression to AR (ROC AUC 0.87) and poor 7-yr graft survival (52% vs. 92%, p=0.003), while BL patients with a high ratio had similar graft survival to patients with NI (91%, p=NS). Thus, progressive early allograft inflammation manifested as BL that progresses to late AR in the first post-transplant year represents a high-risk clinical state for poor allograft outcomes. Such high-risk status can be predicted by the T1B IL-10/TNFα ratio before irreversible scarring sets in, thus allowing timely risk stratification.

Immunoglobulin A nephropathy is characterized by anticommensal humoral immune responses.

IgA nephropathy (IgAN) is a leading cause of kidney failure, yet little is known about the immunopathogenesis of this disease. IgAN is characterized by deposition of IgA in the kidney glomeruli, but the source and stimulus for IgA production are not known. Clinical and experimental data suggest a role for aberrant immune responses to mucosal microbiota in IgAN, and in some countries with high disease prevalence, tonsillectomy is regarded as standard-of-care therapy. To evaluate the relationship between microbiota and mucosal immune responses, we characterized the tonsil microbiota in patients with IgAN versus nonrelated household-matched control group participants and identified increased carriage of the genus Neisseria and elevated Neisseria-targeted serum IgA in IgAN patients. We reverse-translated these findings in experimental IgAN driven by BAFF overexpression in BAFF-transgenic mice rendered susceptible to Neisseria infection by introduction of a humanized CEACAM-1 transgene (B × hC-Tg). Colonization of B × hC-Tg mice with Neisseria yielded augmented levels of systemic Neisseria-specific IgA. Using a custom ELISPOT assay, we discovered anti-Neisseria-specific IgA-secreting cells within the kidneys of these mice. These findings suggest a role for cytokine-driven aberrant mucosal immune responses to oropharyngeal pathobionts, such as Neisseria, in the immunopathogenesis of IgAN. Furthermore, in the presence of excess BAFF, pathobiont-specific IgA can be produced in situ within the kidney.

Outcomes of Continuous Renal Replacement Therapy in a Community Health System.

OBJECTIVE: Continuous renal replacement therapy (CRRT) is commonly used in critically ill, hemodynamically unstable patients with acute kidney injury (AKI). This procedure is resource intensive with reported high in-hospital mortality. We evaluated mortality with CRRT in our healthcare system and markers associated with decreased survival. METHODS: A retrospective cohort study collected data on patients 18 years or older, without prior history of end stage kidney disease (ESKD), who received CRRT in the intensive care units at one of three hospitals in our health system in Columbus, OH from July 1, 2016 to July 1, 2019. Data included demographics, presenting diagnosis, comorbidities, laboratory markers, and patient disposition. In-hospital mortality rates and sequential organ failure assessment (SOFA) scores were calculated. We then compared information between two groups (patients who died during hospitalization and survivors) using univariate comparisons and multivariate logistic regression models. RESULTS: In-hospital mortality was 56.8% (95%CI: 53.4-60.1) among patients who received CRRT. Mean SOFA scores did not differ between survival and mortality groups. The odds for in-patient mortality were increased for patients age ≥60 (OR = 1.74, 95%CI: 1.23-2.44), first bilirubin >2 mg/dL (OR = 1.73, 95%CI: 1.12-2.69), first creatinine < 2 mg/dL (OR = 1.57, 95%CI: 1.04-2.37), first lactate > 2 mmol/L (OR = 2.08, 95%CI: 1.43-3.04). The odds for in-patient mortality were decreased for patients with cardiogenic shock (OR = .32, 95%CI: .17-.58) and hemorrhagic shock (OR = .29, 95%CI: .13-.63). CONCLUSIONS: We report in-hospital mortality rates of 56.8% with CRRT. Unlike prior studies, higher mean SOFA scores were not predictive of higher in-hospital mortality in patients utilizing CRRT.

Intradialytic exercise improves left ventricular mass in hemodialysis patients.

Graham-Brown et al. report the results of a randomized controlled trial in patients on hemodialysis in which a 6-month intradialytic cycling program led to significant reduction in left ventricular mass as compared to the control group. However, there was no significant effect on physical function, physical activity or health-related quality of life.