An Unusual Case of Anti-Glomerular Basement Membrane Disease and Phospholipase A2 Receptor-Associated Membranous Nephropathy After Exposure to Hydrocarbons.

We present a rare case of a patient with toluene exposure manifesting as anti-glomerular basement membrane (GBM) disease on a background of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy. A 23-year-old man presented to the emergency department with hypertension, headache, hemoptysis, anemia, acute kidney injury, glomerular hematuria, and proteinuria. He endorsed repeated exposure to toluene-containing products while repairing dirt bikes. Serologies were positive for anti-GBM antibodies. Kidney biopsy showed crescentic glomerulonephritis with linear immunoglobulin G and granular PLA2R staining by immunofluorescence. He was initially treated with high-dose steroids, plasmapheresis, and hemodialysis for pulmonary-renal syndrome followed by oral cyclophosphamide and prednisone, which were discontinued after 3 months when follow-up biopsies confirmed little chance for renal recovery. He remained on dialysis 1 year later. This case exhibits a unique presentation of anti-GBM syndrome and underlying membranous nephropathy following repeated hydrocarbon exposure. Inhaled toxins promote recurrent localized inflammation, unmasking previously hidden epitopes. Early diagnosis and appropriate use of immunosuppressive and extracorporeal therapies are necessary to prevent morbidity and to improve survival in this rare condition.

Less sodium, more potassium, or both: population-wide strategies to prevent hypertension.

Hypertension is among the most prevalent medical conditions globally and a major contributor to chronic kidney disease, cardiovascular disease, and death. Prevention through nonpharmacological, population-level interventions is critically needed to halt this worldwide epidemic. However, there are ongoing disagreements as to where public policy efforts should focus. Recently the Salt Substitute and Stroke Study demonstrated the efficacy of substituting table salt with potassium salt to reduce the risk of stroke, major cardiovascular events, and death. However, this sparked debate over whether sodium or potassium should be prioritized in countries where table salt substitution was less feasible. In this commentary, we summarize arguments in favor of either strategy: reduced sodium or increased potassium intake. Moreover, we discuss evidence and policy approaches related to either or combined approaches relevant to cultural context. Ultimately, there is an urgent need for policies that both reduce sodium and increase potassium intake; however, identifying a strategy that fits cultural context will be key to improve population-wide blood pressures.

Nephrotoxicity of Antimicrobials and Antibiotics.

Medication-induced nephrotoxicity remains one of the most common causes of acute kidney injury (AKI) among hospitalized patients. Within the extensive group of medications associated with AKI, antibiotics and other antimicrobials are well recognized triggers of structural and functional renal impairment. Clinical manifestations range from mild forms of tubular injury to significant deterioration of kidney function requiring acute renal replacement therapy. Several mechanisms are described, although the most frequent are acute interstitial nephritis, acute tubular necrosis, intratubular crystal deposition, and proximal/distal tubulopathy with electrolyte wasting abnormalities. General risk factors for antimicrobial-induced AKI include pre-existing chronic kidney disease, and concomitant use of medication with nephrotoxic potential. Prevention and early recognition of AKI represent the standard approach to mitigate AKI and avoid morbidity.

Renal Function Decline in Latinos With Type 2 Diabetes.

INTRODUCTION: Diabetic nephropathy remains a highly prevalent microvascular complication in individuals with type 2 diabetes mellitus (T2DM). Hispanic individuals are at increased risk of metabolic and cardiovascular complications compared with non-Hispanic white individuals. We described the long-term kidney outcomes using a culturally based approach to diabetes management in Hispanic patients implemented by the Joslin Diabetes Center's Latino Diabetes Initiative. METHODS: Our retrospective study included 594 Hispanic patients evaluated at the Joslin Diabetes Center from July 2002 to July 2015. Demographic and clinical data were collected from the outpatient visits. RESULTS: Uncontrolled high blood pressure (hazard ratio [HR]: 1.72; 95% confidence interval [CI]:1.18-2.51; P = 0.005), overweight (HR: 2.68; 95% CI: 1.13-6.38; P = 0.026), and longstanding T2DM duration (HR: 1.11; 95% CI: 1.08-1.14; P < 0.0001) at baseline were significantly associated with increased risk of chronic kidney disease (CKD). Although poor glycemic control (HR: 1.18; 95% CI: 1.099-1.258; P < 0.0001), systolic blood pressure (SBP) >140 (HR: 1.01; 95% CI: 1.006-1.02; P = 0.0002), and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use (HR: 1.53; 95% CI: 1.03-2.29; P = 0.04) were significantly associated with increased CKD incidence during follow-up. Interestingly, statin use was associated with lower CKD incidence during the follow-up (HR: 0.52; 95% CI: 0.42-0.65; P < 0.0001). The annual rate of renal function decline in our cohort was estimated to be -1.39 ml/min per 1.73 m2. CONCLUSION: Renal function decline in Latinos is associated with expected but modifiable variables, such as uncontrolled diabetes, uncontrolled hypertension, and being overweight. However, the annual rate of renal function decline in our cohort was estimated to be comparatively higher than previous reports in Hispanic individuals without T2DM, and the general US population with T2DM, but lower than expected for this high-risk group. We highlight the importance of a culturally based patient-centered therapeutic approach to improve long-term outcomes in Hispanic patients at high risk of CKD.

Fructosuria and recurrent hypoglycemia in a patient with a novel c.1693T>A variant in the 3' untranslated region of the aldolase B gene.

Hereditary fructose intolerance, caused by mutations in the ALDOB gene, is an unusual cause of hypoglycemia. ALDOB encodes the enzyme aldolase B, responsible for the hydrolysis of fructose 1-phosphate in the liver. Here, we report the case of a 33-year-old female patient who consulted due to repetitive episodes of weakness, dizziness and headache after food ingestion. An ambulatory 72-h continuous glucose monitoring revealed multiple short hypoglycemic episodes over the day. After biochemical exclusion of other endocrine causes of hypoglycemia, hereditary fructose intolerance seemed a plausible diagnosis. Repeated measurements of urinary fructose revealed pathologic fructosuria, but genetic testing for the three most common mutations in ALDOB resulted negative. We decided to perform complete Sanger sequencing of the ALDOB gene and encountered a variant consisting of a T>A substitution in position 1963 of the ALDOB transcript (c.1693T>A). This position is located within the 3' untranslated region of exon 9, 515 nucleotides downstream the stop codon. After complete withdrawal of dietary fructose and sucrose, the patient presented no new hypoglycemic episodes.

A method to reduce variability in scoring antibody-mediated rejection in renal allografts: implications for clinical trials - a retrospective study.

Poor reproducibility in scoring antibody-mediated rejection (ABMR) using the Banff criteria might limit the use of histology in clinical trials. We evaluated the reproducibility of Banff scoring of 67 biopsies by six renal pathologists at three institutions. Agreement by any two pathologists was poor: 44.8-65.7% for glomerulitis, 44.8-67.2% for peritubular capillaritis, and 53.7-80.6% for chronic glomerulopathy (cg). All pathologists agreed on cg0 (n = 20) and cg3 (n = 9) cases, however, many disagreed on scores of cg1 or cg2. The range for the incidence of composite diagnoses by individual pathologists was: 16.4-22.4% for no ABMR; 17.9-47.8% for active ABMR; and 35.8-59.7% for chronic, active antibody-mediated rejection (cABMR). A "majority rules" approach was then tested in which the scores of three pathologists were used to reach an agreement. This increased consensus both for individual scores (ex. 67.2-77.6% for cg) and for composite diagnoses (ex. 74.6-86.6% cABMR). Modeling using these results showed that differences in individual scoring could affect the outcome assessment in a mock study of cABMR. We conclude that the Banff schema has high variability and a majority rules approach could be used to adjudicate differences between pathologists and reduce variability in scoring in clinical trials.

The Phospholipid Linoleoylglycerophosphocholine as a Biomarker of Directly Measured Insulin Resistance.

BACKGROUND: Plasma concentrations of some lysophospholipids correlate with metabolic alterations in humans, but their potential as biomarkers of insulin resistance (IR) is insufficiently known. We aimed to explore the association between plasma linoleoylglycerophosphocholine (LGPC) and objective measures of IR in adults with different metabolic profiles. METHODS: We studied 62 men and women, ages 30 to 69 years, (29% normal weight, 59% overweight, 12% obese). Participants underwent a 5-point oral glucose tolerance test (5p-OGTT) from which we calculated multiple indices of IR and insulin secretion. Fifteen participants additionally underwent a hyperinsulinemic-euglycemic clamp for estimation of insulin-stimulated glucose disposal. Plasma LGPC was determined using high performance liquid chromatography/time-of-flight mass spectrometry. Plasma LGPC was compared across quartiles defined by the IR indices. RESULTS: Mean LGPC was 15.4±7.6 ng/mL in women and 14.1±7.3 ng/mL in men. LGPC did not correlate with body mass in-dex, percent body fat, waist circumference, blood pressure, glycosylated hemoglobin, log-triglycerides, or high density lipoprotein cholesterol. Plasma LGPC concentrations was not systematically associated with any of the studied 5p-OGTT-derived IR indices. However, LGPC exhibited a significant negative correlation with glucose disposal in the clamp (Spearman r=-0.56, P=0.029). Despite not being diabetic, participants with higher plasma LGPC exhibited significantly higher post-challenge plasma glucose excursions in the 5p-OGTT (P trend=0.021 for the increase in glucose area under the curve across quartiles of plasma LGPC). CONCLUSION: In our sample of Latino adults without known diabetes, LGPC showed potential as a biomarker of IR and impaired glucose metabolism.