Circulating Plasma Biomarkers in Biopsy-Confirmed Kidney Disease.

BACKGROUND AND OBJECTIVES: Biomarkers for noninvasive assessment of histopathology and prognosis are needed in patients with kidney disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using a proteomics assay, we measured a multimarker panel of 225 circulating plasma proteins in a prospective cohort study of 549 individuals with biopsy-confirmed kidney diseases and semiquantitative assessment of histopathology. We tested the associations of each biomarker with histopathologic lesions and the risks of kidney disease progression (defined as ≥40% decline in eGFR or initiation of KRT) and death. RESULTS: After multivariable adjustment and correction for multiple testing, 46 different proteins were associated with histopathologic lesions. The top-performing markers positively associated with acute tubular injury and interstitial fibrosis/tubular atrophy were kidney injury molecule-1 (KIM-1) and V-set and Ig domain-containing protein 2 (VSIG2), respectively. Thirty proteins were significantly associated with kidney disease progression, and 35 were significantly associated with death. The top-performing markers for kidney disease progression were placental growth factor (hazard ratio per doubling, 5.4; 95% confidence interval, 3.4 to 8.7) and BMP and activin membrane-bound inhibitor (hazard ratio, 3.0; 95% confidence interval, 2.1 to 4.2); the top-performing markers for death were TNF-related apoptosis-inducing ligand receptor-2 (hazard ratio, 2.9; 95% confidence interval, 2.0 to 4.0) and CUB domain-containing protein-1 (hazard ratio, 2.4; 95% confidence interval, 1.8 to 3.3). CONCLUSION: We identified several plasma protein biomarkers associated with kidney disease histopathology and adverse clinical outcomes in individuals with a diverse set of kidney diseases. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_12_28_CJN09380721.mp3.

Nephrologists' Attitudes Toward Native Kidney Biopsy: A Qualitative Study.

RATIONALE & OBJECTIVE: Although kidney biopsy is a useful tool, nephrologists' approach toward biopsies is inconsistent for reasons incompletely understood, including lack of established clinical guidelines. We examined contemporary clinical decision-making patterns among nephrologists to perform native kidney biopsy. STUDY DESIGN: Qualitative study using semistructured interviews. SETTING & PARTICIPANTS: Purposive sampling was used to select nephrologists from different regions in the United States. Semistructured interviews were continued until thematic saturation. ANALYTICAL APPROACH: A modified grounded theory was used to identify dominant themes reflecting the nephrologists' decision-making styles about kidney biopsy. RESULTS: Twenty nephrologists were interviewed: 16 (80%) were from academic centers, 3 (15%) performed their own biopsies, and 7 (35%) had been in practice for less than 10 years. The median time of practice was 14 years. We found substantial variability among the nephrologists in their attitude toward using kidney biopsy, which reflected individual differences in weighing the risks and benefits of the procedure for an individual patient. Five overarching themes were identified: operator comfort with biopsy and availability of interventional radiologist, exposure to biopsy during training and years of experience, concerns about the invasiveness of biopsy and inflicting harm, perception of evidence base and limited treatment options, and patient characteristics and preference. LIMITATIONS: Generalizability was limited because the nephrologists sampled may not have been broadly representative. CONCLUSIONS: Multiple factors influence nephrologists' decision to pursue kidney biopsy, with substantial variability among nephrologists that can have meaningful clinical implications. This suggests the need to establish consensus guidelines to make biopsy practice more standardized.

A Case of False-Positive HIV Test in a Patient With Newly Diagnosed Hodgkin Lymphoma and Literature Review.

Hodgkin lymphoma (HL) is one of the non-acquired immunodeficiency syndrome (AIDS)-defining cancers (NADCs). HIV testing has become a part of routine testing in HL because of commonly anticipated association. Here we report an unusual case where the need for HIV screening in a newly diagnosed case of HL raised an ethical dilemma and a medical challenge due to false-positive HIV test results. In literature, pregnancy, autoimmune disorders, some viral infections, and the presence of hypergammopathy of hematologic malignancy have all been linked with false-positive HIV screening. The reactive results require additional testing with an HIV-1/HIV-2 antibody differentiation assay. The specimens show reactivity on the initial screening immunoassay, but negative or indeterminate antibody differentiation assay should undergo nucleic acid testing. Nevertheless, several instances of discordance between screening and confirmatory techniques have been described. It is speculated that this might be due to coincidental cross-reaction of subtypes of polyclonal gamma globulin with the HIV p24 antigen. In conclusion, this case signifies the understanding of the HIV testing algorithm and the use of reflex testing in the context of a positive HIV test before disclosing such preliminary results to patients and/or physicians.

Bleeding Complications After Percutaneous Native Kidney Biopsy: Results From the Boston Kidney Biopsy Cohort.

BACKGROUND: The major risk of kidney biopsy is severe bleeding. Numerous risk factors for bleeding after biopsy have been reported, but findings have been inconsistent. METHODS: We retrospectively reviewed medical records of adult patients enrolled in a native kidney biopsy cohort study to identify major bleeding events (red blood cell [RBC] transfusions, invasive procedures, kidney loss, or death). We used logistic and linear regression models to identify characteristics associated with postbiopsy RBC transfusions and decline in hemoglobin within a week after the procedure. RESULTS: Major bleeding events occurred in 28 of 644 (4.3%) patients (28 required an RBC transfusion, 4 underwent angiographic intervention, and 1 had open surgery to control bleeding). No patient lost a kidney or died because of the biopsy. Postbiopsy RBC transfusion risk was driven by the baseline hemoglobin level (odds ratio [OR] 13.6; 95% confidence interval [CI] 5.4-34.1 for hemoglobin <10 vs. ≥10 g/dl). After adjusting for hemoglobin, no other patient characteristics were independently associated with RBC transfusions. Female sex (ß = 0.18; 95% CI: 0.04-0.32), estimated glomerular filtration rate (eGFR) <30 ml/min per 1.73 m2 (ß = 0.32; 95% CI: 0.14-0.49), and baseline hemoglobin (ß = 0.09; 95% CI: 0.05-0.13, per g/dl increase) were independently associated with a larger drop in hemoglobin. Histopathologic lesions were not independently associated with major bleeding after biopsy. CONCLUSION: Biopsies were generally well tolerated. Baseline hemoglobin was the dominant risk factor for RBC transfusions, but female sex and eGFR <30 ml/min per 1.73 m2 were also associated with a larger decline in hemoglobin after the procedure.

Muscle mass, BMI, and mortality among adults in the United States: A population-based cohort study.

BACKGROUND: The level of body-mass index (BMI) associated with the lowest risk of death remains unclear. Although differences in muscle mass limit the utility of BMI as a measure of adiposity, no study has directly examined the effect of muscle mass on the BMI-mortality relationship. METHODS: Body composition was measured by dual-energy x-ray absorptiometry in 11,687 participants of the National Health and Nutrition Examination Survey 1999-2004. Low muscle mass was defined using sex-specific thresholds of the appendicular skeletal muscle mass index (ASMI). Proportional hazards models were created to model associations with all-cause mortality. RESULTS: At any level of BMI ≥22, participants with low muscle mass had higher body fat percentage (%TBF), an increased likelihood of diabetes, and higher adjusted mortality than other participants. Increases in %TBF manifested as 30-40% smaller changes in BMI than were observed in participants with preserved muscle mass. Excluding participants with low muscle mass or adjustment for ASMI attenuated the risk associated with low BMI, magnified the risk associated with high BMI, and shifted downward the level of BMI associated with the lowest risk of death. Higher ASMI was independently associated with lower mortality. Effects were similar in never-smokers and ever-smokers. Additional adjustment for waist circumference eliminated the risk associated with higher BMI. Results were unchanged after excluding unintentional weight loss, chronic illness, early mortality, and participants performing muscle-strengthening exercises or recommended levels of physical activity. CONCLUSIONS: Muscle mass mediates associations of BMI with adiposity and mortality and is inversely associated with the risk of death. After accounting for muscle mass, the BMI associated with the greatest survival shifts downward toward the normal range. These results provide a concrete explanation for the obesity paradox.

Correction: Muscle mass, BMI, and mortality among adults in the United States: A population-based cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0194697.].

Persistent hematuria caused by renal cell carcinoma after aortic valve replacement and warfarin therapy.

Hematuria is a common finding in renal cell carcinoma, and persistent hematuria, even in those receiving anticoagulation, warrants workup. We present a case of a patient with persistent hematuria who was found to have a renal mass that was not evident on renal ultrasound and computed tomography of the abdomen and pelvis but was seen on magnetic resonance imaging.

Sarcopenia, obesity, and mortality in US adults with and without chronic kidney disease.

INTRODUCTION: In pre-dialysis chronic kidney disease (CKD), the association of muscle mass with mortality is poorly defined, and no study has examined outcomes related to the co-occurrence of low muscle mass and excess adiposity (sarcopenic-obesity). Methods: We examined abnormalities of muscle and fat mass in adult participants of the National Health and Nutrition Examination Survey 1999-2004. We determined whether associations of body composition with all-cause mortality differed between participants with CKD compared to those without. RESULTS: CKD modified the association of body composition with mortality (p=0.01 for interaction). In participants without CKD, both sarcopenia and sarcopenic obesity were independently associated with increased mortality compared with normal body composition (hazard ratio (HR) 1.44 (95%CI 1.07-1.93) and 1.64 (95%CI 1.26-2.13), respectively). These associations were not present among participants with CKD. Conversely, obese persons had the lowest adjusted risk of death, with an increased risk among those with sarcopenia (HR 1.43 (95%CI 1.05-1.95)) but not sarcopenic-obesity (p=0.003 for interaction by CKD status; HR 1.21 (95%CI 0.89-1.65)), compared with obesity. CONCLUSION: Sarcopenia associates with increased mortality regardless of eGFR, but excess adiposity modifies this association among people with CKD. Future studies of prognosis and weight loss and exercise interventions in CKD patients should consider muscle mass and adiposity together rather than in isolation.

Symptomatic Diverticular Disease in Patients With Severely Reduced Kidney Function: Higher Rates of Complications and Transfusion Requirement.

BACKGROUND: The prevalence of diverticulosis is increasing with 5-10% of patients developing diverticulitis and 5-15% developing symptomatic bleeding. Diverticulitis can result in abscess, perforation, fistula, or obstruction. Bleeding has combined morbidity and mortality rates of 10-20%. The purpose of this study was to compare diverticulitis-related complications and transfusion requirements for diverticular bleeding in patients with normal to moderately reduced kidney function (glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2) and patients with severe renal impairment (GFR < 30 mL/min/1.73 m2), and identify factors associated with these outcomes. METHODS: We retrospectively reviewed records of all patients with diverticulitis and diverticular bleeding treated at our hospital from January 1, 2011 to July 31, 2016. Patients were evaluated for baseline characteristics, GFR, baseline hemoglobin, medications, comorbidities, length of stay (LOS), presence of perforations or abscesses and the need for transfusion. RESULTS: Of the 291 patients included, males were 167 (58%). Perforations and abscesses complicating diverticulitis developed in 31/136 (23%) of patients with GFR ≥ 30 mL/min/1.73 m2, and in 13/26 (50%) of patients with GFR < 30 mL/min/1.73 m2 (odds ratio (OR): 3.4; 95% confidence interval (CI): 1.423 - 8.06; P = 0.0073). Mean LOS (days) was 6.3 ± 4 in the GFR ≥ 30 mL/min/1.73 m2 group and 8.5 ± 4.4 in GFR < 30 mL/min/1.73 m2 group (P = 0.0001). Blood transfusion for diverticular bleeding occurred in 11/78 (14%) of patients with GFR ≥ 30 mL/min/1.73 m2 and in 22/51 (43%) of patients with GFR < 30 mL/min/1.73 m2 (OR: 4.6; 95% CI: 1.99 - 10.76; P = 0.0004). Among patients who needed transfusion, mean LOS was 8.5 ± 2.5 in GFR ≥ 30 mL/min/1.73 m2 group and 9 ± 5 in those with GFR < 30 mL/min/1.73 m2 (P = 0.04). There were no differences in age, gender or race between the study groups. CONCLUSION: There was a significant increase in complicated diverticulitis cases, transfusion requirements for diverticular bleeding and LOS in patients with severely reduced kidney function compared to patients with normal-moderately reduced renal function.

Dietary acid, age, and serum bicarbonate levels among adults in the United States.

BACKGROUND AND OBJECTIVES: Greater dietary acid has been associated with lower serum bicarbonate levels in patients with CKD. Whether this association extends to the general population and if it is modified by age are unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study examined the association of the dietary acid load, estimated by net endogenous acid production, with serum bicarbonate levels in adult participants in the National Health and Nutrition Examination Survey 1999-2004. RESULTS: The mean serum bicarbonate was 24.9 mEq/L (SEM=0.1), and the mean estimated net endogenous acid production was 57.4 mEq/d (SEM=0.4). Serum bicarbonate was linearly associated with age, such that the oldest participants had the highest serum bicarbonate levels. After multivariable adjustment, participants in the highest quartile of net endogenous acid production had 0.40 mEq/L (95% confidence interval, -0.55 to -0.26) lower serum bicarbonate and a 33% (95% confidence interval, 3 to 72) higher likelihood of acidosis compared with those participants in the lowest quartile. There was a significant interaction by age of the association of net endogenous acid production with serum bicarbonate (P=0.005). Among participants 20-39, 40-59, and ≥60 years old, those participants in the highest net endogenous acid production quartile had 0.26 (95% confidence interval, -0.49 to -0.03), 0.60 (95% confidence interval, -0.92 to -0.29), and 0.49 (95% confidence interval, -0.84 to -0.14) mEq/L lower serum bicarbonate, respectively, compared with participants in the lowest quartile. CONCLUSION: Greater dietary acid is associated with lower serum bicarbonate in the general US population, and the magnitude of this association is greater among middle-aged and elderly persons than younger adults.