Glomerulonephritis

Each participating center will enroll approximately 250 consecutive individuals over a 5-year period from 2011 until 2015, totaling 2,450 adult patients with CKD who provide written informed consent. The participating individuals will be monitored for approximately 10 years until death or until ESRD occurs.
The KNOW-CKD will enroll ethnic Korean patients with CKD who range in age between 20 years and 75 years. The CKD stages from 1 to 5 (predialysis), based on the eGFR, is calculated using the four-variable Modification of Diet in Renal Disease (MDRD) equation as follows:
eGFR (ml/min per 1.73 m²) = 175 × [serum Cr (mg/dl)] ^-1.154 × [age]^-0.203 × [0.742 if female] × [1.212 if black], using serum creatinine concentrations measured at a central laboratory and an assay traceable to the international reference material [12 (link)].
Excluded subjects are those who 1) are unable or unwilling to give written consent, 2) have previously received chronic dialysis or organ transplantation, 3) have heart failure (NYHA class 3 or 4) or liver cirrhosis (Child-Pugh class 2 or 3), 4) have a past or current history of malignancy, 5) are currently pregnant, or 6) have a single kidney due to trauma or kidney donation.
We defined and allocated the specific causes of the CKD into four subgroups: glomerulonephritis (GN), diabetic nephropathy (DN), hypertensive nephropathy (HTN), and polycystic kidney disease (PKD). The definition of the subgroup is defined by the pathologic diagnosis, in the event that the biopsy result is available. Otherwise, the subgroup classification depends on the clinical diagnosis. GN is defined by the presence of glomerular hematuria or albuminuria with or without an underlying systemic disease causing glomerulonephritis. The diagnosis of DN is based on albuminuria in a subject with type 2 diabetes mellitus and the presence of diabetic retinopathy. HTN is defined by the patient’s hypertension history and the absence of a systemic illness associated with renal damage. Unified ultrasound criteria [13 (link)] will be used to diagnose PKD. The other causative diseases will be categorized as ‘unclassified’.

From January 2015 to August 2019 we prospectively recruited patients attending the peripheral nerve clinic in the John Radcliffe Hospital (Oxford, UK) with either confirmed or suspected inflammatory neuropathy to an observational study (Research Ethics Committee approval number 14/SC/0280). These patients provided informed written consent. Serum samples from these patients, and patients with suspected inflammatory neuropathies, received by our laboratory for diagnostic testing between August 2017 and August 2019. were screened for antibodies against paranodal (CNTN1, contactin-associated protein 1—Caspr1, neurofascin 155—NF155) and nodal (NF140/186) antigens.
To investigate whether CNTN1 antibodies might be more widely associated with nephrotic syndrome caused by idiopathic MGN itself, we examined 295 serum samples from patients with idiopathic membranous nephropathy, collected as part of the MRC Glomerulonephritis bank [14 (link)].
Serum samples from 70 patients with other antibody-mediated CNS neurological disorders, 20 with multiple sclerosis, 120 individuals without neurological disease, and 46 patients with lupus nephritis, including pure class V membranous lupus nephritis, were also obtained as controls (S1 Fig).
Information that could identify individual participants was stored confidentially and only accessible at the time of data collection to treating physicians, or those with necessary ethical approval and Good Clinical Practice (GCP) training. Data was subsequently de-identified.

Demographic characteristics and complications were recorded, including age, sex, body mass index (BMI), education level, dialysis duration, systolic blood pressure, diastolic blood pressure, pulse pressure, smoking, diabetes mellitus, hypertension, primary kidney disease, and history of CVD. Education level was recorded as the highest school level for which a diploma was obtained: primary school or below, middle school, high school and beyond. Primary kidney disease includes chronic glomerulonephritis, diabetic nephropathy, and others (such as IgA nephropathy, nephrotic syndrome, lupus nephritis, Sjogren's syndrome, and ANCA-associated vasculitis). CVD information was obtained from medical history reviews, and CVD was recorded if any of the following conditions were present: angina pectoris, grade III or IV congestive heart failure (as classified based on the guidelines of the New York Heart Association), transient ischemic attack, myocardial infarction, and cerebrovascular accident.

Approval for this study was obtained from the University of Southern California Institutional Review Board (HS-12-00383). Procedures were followed in accordance with the ethical standards of the University of Southern California Institutional Review Board and with the Declaration of Helsinki of 1975, as revised in 2000. Written informed consent was not required for the ultrasound procedure since this was performed for clinical purposes, as was subsequent volume management, and data collection was retrospective.
Adult patients hospitalized between 1 August 2012 and 28 February 2020, with AKI, cirrhosis and ascites, who had an IVC US performed, were evaluated for HRS-AKI defined by current criteria [1 ]. Eighty-three patients were retrieved from the daily renal consult rounding lists of the primary investigator (Figure 1). Initial exclusion criteria adapted from the Practice Guidelines by the American Association for the Study of Liver Diseases [1 ] included documentation of potential causes of AKI other than HRS-AKI such as: (1) recent cardiopulmonary arrest, hypotension with vasopressor support, (2) current or recent use of nephrotoxic agents, (3) evidence of glomerulonephritis or interstitial nephritis, and/or (4) urinary tract obstruction. Other exclusion criteria included: (5) IVC thrombosis, (6) CKD stage 4 or 5 or maintenance dialysis therapy prior to or at the time of IVC US, (7) preexisting acute decompensated heart failure or severe cardiac valvular disease, which may alter IVC US findings [10 (link)] and also impair renal function, and/or (8) patients who had not received the standardized albumin administration and diuretic withdrawal prior to the IVC US. Thirty one patients were excluded based on these criteria.
The remaining 52 patients without exclusion criteria clearly documented on the rounding lists were further evaluated by detailed chart review for the presence of any of the above listed plus additional exclusion criteria (Figure 1). Thirty-two more patients were excluded due to these exclusion criteria: (1) follow-up for <3 days after the IVC US since they may not have had time to receive or respond to the volume management recommendations, (2) had recently received hemodialysis therapy, (3) did not have a documented baseline serum creatinine value, (4) had urinary retention documented by bladder catheterization, and/or (5) had tense ascites and IAH with bladder pressures >12 mmHg [6 (link)].
The remaining 20 patients also had to have a persistent increase in serum creatinine of ≥ 0.3 mg/dL within 2 days of onset of AKI or alternately an increase in serum creatinine of ≥50% from a baseline value documented within the prior 90 days, and failure of serum creatinine to persistently decrease ≥0.3 mg/dL after at least 2 days of diuretic withdrawal and a trial of volume expansion with albumin (1 g/kg of body weight per day to a maximum of 100 g/day) [1 ]. These 20 patients, who met the above criteria for HRS-AKI (Figure 1) and had received volume expansion and diuretic withdrawal prior to the IVC US examination, had been presumed to be intravascularly replete by the primary team.