ANCA vasculitis presenting with acute interstitial nephritis without glomerular involvement.

ANCA-associated vasculitis (AAV) with renal involvement typically causes pauci-immune glomerulonephritis. We present a case of acute interstitial nephritis (AIN) as the sole renal lesion without glomerulonephritis with myeloperoxidase (MPO) AAV. A 45-year-old female with history of Crohn's disease, gastroesophageal reflux disease (GERD) with Barrett's esophagus, pulmonary embolism, and polyarthralgias was evaluated in nephrology clinic in 2018. AIN without glomerulonephritis was first diagnosed in 2011 on renal biopsy. p-ANCA was positive with MPO titer of > 100 U/mL. Serum creatinine improved from 2.1 to 0.9 mg/dL with prednisone and azathioprine. Repeat biopsy in 2013 for worsening renal function showed AIN without glomerular involvement. Serum creatinine improved from 1.9 to 1.2 mg/dL with prednisone and cyclosporine. Crohn's disease was diagnosed in 2014. AIN was attributed to Crohn's, and cyclosporine was stopped in 2016. Adalimumab was started in 2016, without improvement in renal function or urine sediment. Attempt was made to switch proton pump inhibitor (PPI) to H2-blocker, but the latter was not tolerated. Repeat biopsy in 2/2018 showed AIN with severe fibrosis and tubular atrophy and glomerulosclerosis but no active glomerular disease. MPO titers remained high at 132 U/mL. Mycophenolic acid and prednisone were started without response, followed by rituximab for AAV-associated AIN. Serum creatinine worsened to 6.0 mg/dL in 9/2018, with plan to start peritoneal dialysis. AAV may present with isolated AIN without glomerular involvement. The rarity of this presentation may contribute to delay in appropriate management. Alternative explanations for AIN, such as Crohn's disease or PPI use should be considered with caution in the setting of high-titer ANCA positivity.

Kidney transplant recipients with polycystic kidney disease have a lower risk of post-transplant BK infection than those with end-stage renal disease due to other causes.

BACKGROUND: Polyomavirus-associated nephropathy is associated with high risk of kidney allograft loss. Whether the cause of native end-stage renal disease influences the risk of BK infection is unclear. METHODS: A retrospective, single-center study of 2741 adult kidney transplant recipients between 1994 and 2014 was performed. Recipients had end-stage renal disease due to polycystic kidney disease (PKD, n = 549), diabetes mellitus (DM, n = 947), hypertension (HTN, n = 442), or glomerulonephritis (GN, n = 803). RESULTS: A total of 327 recipients (12%) developed post-transplant BK viremia over a median follow-up time of 5 years. The incidence rate of BK viremia was lowest in patients with PKD (1.46 per 100 person-years) compared to other causes of ESRD (DM = 2.06, HTN = 2.65, and GN = 2.01 per 100 person-years). A diagnosis of PKD was associated with a lower risk of post-transplant BK viremia (adjusted HR (95% CI) = 0.67 (0.48-0.95), P = 0.02). BK nephropathy was significantly less common in patients with PKD (0.21 per 100 person-years) compared to those with HTN (0.80 per 100 person-years, P ≤ 0.001). Among patients with PKD, the risk of BK viremia was lower in patients with nephrectomy, compared to those without nephrectomy (adjusted HR (95% CI) = 0.42 (0.19-0.92), P < 0.05). CONCLUSION: ESRD due to PKD is associated with a lower risk of post-transplant BK infection. The renal tubular epithelial cells in PKD are unique; they are in a proliferative but non-differentiated state. Whether this characteristic of renal tubular epithelial cells alters the BK viral reservoir or replication in PKD patients warrants further study.

Demographic and Behavioral Predictors of Severe Fetomaternal Hemorrhage: A Case-Control Study.

BACKGROUND: Fetomaternal hemorrhage (FMH) signifies failure of the placental barrier with whole blood transfer. Fetal anemia following FMH is associated with significant morbidity and mortality. If FMH is identified early, fetal anemia can be treated to minimize adverse outcomes. Risk factors for FMH are not known, limiting efforts to provide targeted screening for FMH. OBJECTIVE: To identify maternal and/or pregnancy characteristics associated with FMH that are recognizable prior to fetal morbidity. METHODS: This is the first published case-control study of FMH. Cases were identified from a prospectively maintained database of all hospital births between 1988 and 2010. Each case was matched to 4 controls by date and time of birth, allowing for assessment of a wide range of clinical and demographic data. Logistic regression modeling was used to assess the association between demographic and clinical characteristics and the diagnosis of FMH. RESULTS: A total of 23 mother-baby pairs impacted by FMH and 92 matched controls were evaluated. Compared to controls, case mothers were more likely to have private insurance and to work outside the home and at night during pregnancy. Cases were more likely to be delivered preterm, but preterm labor was not more common among cases. There was no difference in race/ethnicity of cases compared to controls. CONCLUSIONS: Severe FMH is associated with significant morbidity and mortality of the affected neonate. Women with FMH were more likely to work outside the home during pregnancy than women with normal pregnancies. This finding has implications for third-trimester screening of pregnant women who work in strenuous fields.

Impact of physician awareness on diagnosis of fetomaternal hemorrhage.

BACKGROUND: Fetomaternal hemorrhage (FMH) is a poorly understood condition in which the placenta allows transmission of fetal whole blood to the mother. FMH can cause fetal anemia resulting in critical illness, death or lifelong disability. Ascertainment of the incidence of FMH is limited by reliance on retrospective studies that are dependent on a diagnosis of FMH being made at the time of patient presentation. OBJECTIVE: To determine whether the diagnosis of FMH is made more frequently after an educational intervention to increase physician awareness of the condition. METHODS: This is a retrospective cohort study of all neonates born at our institution from 1988 through 2010. The medical records of all neonates diagnosed with anemia in the first 24 h of life were reviewed. The incidence of FMH as a documented etiology of anemia was compared between infants born before and after our educational intervention. RESULTS: Of 124,738 births during the study period, 572 neonates with neonatal anemia were identified. A total of 23 cases of FMH demonstrated by positive Kleihauer-Betke testing occurred in our cohort. The incidence of diagnosed FMH prior to our intervention was 22 per 1,000 anemic neonates compared to 182 per 1,000 afterwards (p < 0.001), while the incidence of neonatal anemia remained unchanged (p = 0.377). CONCLUSIONS: FMH may be a significant cause of neonatal anemia. Diagnosis of FMH is highly dependent on physician awareness of the condition. Incorrect or absent diagnosis of the etiology of neonatal anemia has significant implications for our understanding of the epidemiology of FMH.

Evidence that a late-emerging population of trunk neural crest cells forms the plastron bones in the turtle Trachemys scripta.

The origin of the turtle plastron is not known, but these nine bones have been homologized to the exoskeletal components of the clavicles, the interclavicular bone, and gastralia. Earlier evidence from our laboratory showed that the bone-forming cells of the plastron were positive for HNK-1 and PDGFRalpha, two markers of the skeletogenic neural crest. This study looks at the embryonic origin of these plastron-forming cells. We show that the HNK-1+ cells are also positive for p75 and FoxD3, confirming their neural crest identity, and that they originate from the dorsal neural tube of stage 17 turtle embryos, several days after the original wave of neural crest cells have migrated and differentiated. DiI studies show that these are migratory cells, and they can be observed in the lateral regions of the embryo and can be seen forming intramembranous bone in the ventral (plastron) regions. Before migrating ventrally, these late-emerging neural crest cells reside for over a week in a carapacial staging area above the neural tube and vertebrae. It is speculated that this staging area is where they lose the inability to form skeletal cells.