Acute Interstitial Nephritis Induced by Clozapine.

Acute interstitial nephritis (AIN) classically presents as acute kidney injury most often induced by offending drugs. Less frequently it is secondary to infections, autoimmune disorders, or idiopathic conditions. Development of drug-related AIN is not dose dependent and a recurrence can occur with re-exposure to the drug. We present a 50-year-old male with treatment resistant schizoaffective disorder who developed clozapine-induced AIN, confirmed with kidney biopsy within 2 months of taking this medication. His kidney function improved with removal of the drug and treatment with steroids. However, his kidney function was again significantly impaired when rechallenged with even a lower dose of clozapine a year later. Kidney function returned to baseline after stopping clozapine. Monitoring of kidney function during clozapine therapy is essential to therapy. Prompt diagnosis is imperative as discontinuation of offending agent can prevent acute kidney injury.

COVID-19 and APOL-1 High-Risk Genotype-Associated Collapsing Glomerulonephritis.

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the lungs and can lead to acute respiratory distress syndrome (ARDS). The ongoing global pandemic has created healthcare and economic crisis for almost every nation of the world. Though primarily affecting the lungs, it has also affected the kidney in various ways including acute kidney injury (AKI), proteinuria, and hematuria. It has been increasingly shown that African American (AA) individuals affected with COVID-19 and presenting with AKI and nephrotic-range proteinuria are very susceptible to focal segmental glomerulosclerosis (FSGS). The APOL-1 gene, associated with the African American population, has been increasingly recognized as a risk factor for FSGS affected with COVID-19. Our case highlights a similar case of COVID-19 in a 65-year-old AA descendant with biopsy-proven FSGS and genetically confirmed APOL-1 alleles.

A multi-center retrospective cohort study defines the spectrum of kidney pathology in Coronavirus 2019 Disease (COVID-19).

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19), resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases that have increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%), which was associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19 and demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney.

Factors associated with intradialytic systolic blood pressure variability.

BACKGROUND: Although blood pressure lability during hemodialysis has long been recognized, little is known about factors that promote nonsystematic intradialytic blood pressure variability. STUDY DESIGN: Prospective observational cohort. SETTING & PARTICIPANTS: Random cluster sample of 218 prevalent hemodialysis patients treated at 5 participating DaVita Dialysis units. PREDICTORS: Clinical variables that may plausibly influence intradialytic systolic blood pressure (SBP) variability. OUTCOMES: SBP variability as described by: (1) the deviation of SBP from its anticipated course (primary metric) and (2) the absolute value of the difference between successive SBP measurements (secondary metric). MEASUREMENTS: SBPs measured and recorded (n = 19,170) per clinical protocol during hemodialysis treatments (n = 2,422; median 11 per patient) occurring in the first 30 days of study. Predictors were assessed through standardized interview, examination, and medical record abstraction. RESULTS: Results were similar when SBP variability was considered in terms of the primary and secondary metrics. Older age and longer dialysis vintage were associated with increased SBP variability, whereas other patient characteristics were not. Greater fluid removal during hemodialysis (whether considered as volume or rate either absolute or relative to total-body water) was associated with greater SBP variability independently of its effects on net pre- to posttreatment SBP reduction. Neither number nor dialyzability of antihypertensive medications nor individual classes of agents showed an association with SBP variability. LIMITATIONS: Over-representation of African Americans and patients with congestive heart failure; observational design; use of clinically measured blood pressures; absence of medication adherence confirmation. CONCLUSIONS: Increased intradialytic SBP variability is associated with greater dialytic fluid removal and rate, as well as demographic characteristics, such as older age and dialysis vintage. Further work is needed to confirm these findings and measure associations between SBP variability and clinical outcomes.

A model of systolic blood pressure during the course of dialysis and clinical factors associated with various blood pressure behaviors.

BACKGROUND: Little is known about the behavior of systolic blood pressure (SBP) during hemodialysis. STUDY DESIGN: Prospective observational cohort. SETTING & PARTICIPANTS: 218 prevalent hemodialysis patients treated at 5 participating DaVita Dialysis units. PREDICTORS: Clinical variables that may plausibly influence the behavior of SBP during the course of hemodialysis sessions. OUTCOMES: SBP at the onset of dialysis and its rate of change (slope) over the first 25% and latter 75% of the treatment interval. MEASUREMENTS: SBPs measured and recorded per clinical protocol during the first 30 days of study (median, 11 treatments/patient; SBP measured at 30-minute intervals). RESULTS: Intradialytic SBP behavior is well characterized by a 2-slope linear spline model, which describes SBP at time zero, a rapid decrease during the first 25% of the treatment (early), and a more gradual decrease thereafter (late). Higher ultrafiltration volume and rate each are associated with greater SBP at the start of dialysis and more rapid early and late SBP decreases. Use of a higher number of antihypertensives was associated with greater time zero SBP. Calcium acetate use is associated with high SBP at the start of hemodialysis and a more pronounced decrease during the early and late parts of treatment. LIMITATIONS: Over-representation of blacks and patients with congestive heart failure; observational design; use of clinically measured blood pressures. CONCLUSIONS: Intradialytic SBP can be characterized using 3 parameters: value at the start of dialysis and slopes during the first 25% and latter 75% of treatment. Practices related to fluid management, antihypertensive use, and metabolic bone disease control are associated with blood pressure behavior during dialysis. Further work is needed to confirm findings and measure associations between various aspects of intradialytic blood pressure behavior and clinical outcomes.