Drug-induced interstitial nephritis is a recognized cause of acute and chronic renal failure. Some of them lead to the formation of granulomata. T-cell-mediated immune response is implicated in the pathogenesis. Here, we describe the case of a 74-year-old male patient with metastatic melanoma who was referred to our clinic with a history of rash and worsening renal function. Because of subacute onset, progressively worsening renal function in the presence of skin rash, elevated liver enzymes, and in the background of exposure, medication-induced interstitial nephritis was suspected. He received 3 doses of ipilimumab, a novel drug used in the treatment of metastatic melanoma within 3 months before the onset of renal failure. A renal biopsy was done, which showed granulomatous interstitial nephritis. Renal biopsy findings, temporal relation between renal failure and exposure to medication, and review of the literature supported a diagnosis of ipilimumab-induced renal failure. He was started on steroids, and renal function recovered in the next 1 month. Immune-related adverse reaction is one of the common side effects of ipilimumab. Ipilimumab-induced hepatitis and colitis has been previously reported in the literature. This is the first ever case report of ipilimumab-induced granulomatous interstitial nephritis.
Mortality of patients treated with combined ECMO and CRRT is high. Initiation of CRRT in these patients is simply an indicator of severity of illness and fatality. Younger age, higher arterial pH, left ventricular dysfunction and use of VA ECMO are associated with improved survival in these patients.
Chronic hemodialysis is associated with significant thrombophilia. Of interest, hemodialysis patients have increased carboxyhemoglobin (COHb) and exhaled carbon monoxide (CO), signs of upregulated heme oxygenase (Hmox) activity. Given that CO enhances plasmatic coagulation, we determined whether patients requiring chronic hemodialysis had an increase in endogenous CO, plasmatic hypercoagulability and decreased fibrinolytic vulnerability. Carbon monoxide was determined by noninvasive pulse oximetry measurement of COHb. Blood samples were obtained just before hemodialysis. Thrombelastographic methods to assess plasma coagulation kinetics, fibrinolytic kinetics, and formation of carboxyhemefibrinogen (COHF) were used. Hemodialysis patients (n = 45) had abnormally increased COHb concentrations of 2.2 ± 1.9%, indicative of Hmox upregulation. Coagulation and fibrinolytic parameter normal values were determined with normal individual (n = 30) plasma. Thirty-seven patients of the hemodialysis cohort had COHF formation (82.2%, [67.9%-92.0%]; mean, [95% confidence interval]), and many of this group of patients had abnormally great velocity of clot growth (73.3%, [58.1%-85.4%]) and strength (75.6%, [60.5%-87.1%]). Furthermore, over half of COHF positive patients had a hypofibrinolytic state, evidenced by an abnormally prolonged time to maximum rate of lysis (53.3%, [37.9%-68.6%]) and clot lysis time (64.4%, [48.8%-78.1%]). Carbon monoxide enhanced coagulation and diminished fibrinolytic vulnerability in hemodialysis patients. Future investigation of hemodialysis, CO-related thrombophilia is warranted.
LETTER TO THE EDITOR mL. Subsequently by hospital day 9, oxygen requirements improved to 6 L/min along with improvements in inflammatory markers and CXR infiltrates. On hospital day 11, patient again had increasing oxygen requirements to 11 L/min with up-trending LDH and worsening CXR infiltrates. Given this, a second dose of tocilizumab 400 mg was administered. Following this dose, patient had progressive improvement in hypoxia, inflammatory markers, as well as infiltrates on CXR. Patient was discharged on day 17 of hospitalization on 4 L/min of supplemental oxygen with resolved AKI and transaminitis. Figure 1 summarizes treatment therapies, oxygen requirement, and inflammatory markers during hospital course. Our case illustrated the utility of tocilizumab in treating SARS-CoV-2 induced inflammatory syndrome in a transplant recipient. Further randomized studies are necessary to confirm the benefit, optimal dosing, and timing of administration of IL-6Ra therapies in the management of COVID-19 in transplant recipients.
A 47-year-old African-American male with a history of hypertension for 1 year and cocaine use presented to the emergency department with acute onset of bilateral flank pain, nausea, vomiting, and diarrhea. Physical examination was unremarkable. Laboratory evaluation revealed a white blood count of 15.1 K/ml (normal 4.5-11.5 K/ml) and a serum creatinine of 2.4 mg/100 ml. A non-contrast CT scan of the abdomen was unremarkable. The patient was treated with morphine (for pain) and i.v. fluids, felt better, and was discharged for out-patient follow-up.The patient saw his primary care physician 2 days later (day 3) and reported persistence of the bilateral flank pain. The patient also reported a transient inability to urinate for 36 h before the visit. An abdominal ultrasound and blood chemistry were obtained. On day 5, he was referred by his physician to the emergency department for a serum creatinine of 9.2 mg/100 ml from day 3. At the time of admission, the patient reported using 5-6 g/day of ibuprofen for the previous 4 days and admitted to sniffing cocaine a few hours before the initial onset of flank pain.On physical examination, the patient was a well-built African-American male with a temperature of 99.2 1F, pulse rate of 60/min, blood pressure of 150/85 mm Hg and weight of 85 kg (BMI 27.7 kg/m 2 ). There was no orthostasis, pallor, or skin rash. The heart and lung examinations were unremarkable. The abdomen was soft, with no suprapubic dullness. There was no costovertebral angle tenderness or pitting edema. The extremity pulses were symmetric and equal.Laboratory results are presented in Table 1. Serologic tests for hepatitis B and C viruses, human immunodeficiency virus, antinuclear antibody, and rheumatoid factor were negative. Serum complements, including C3, C4, and CH50, were within the normal range. Hemoglobin electrophoresis, chest X-ray, electrocardiogram, and echocardiogram were unremarkable. Renal ultrasound revealed normal-sized kidneys with mildly increased echogenecity and no hydronephrosis. A 99m Tc-MAG3 (mercaptoacetyltriglycine) radionuclide renogram showed multiple wedge-shaped photopenic areas in both kidneys (Figure 1a). Owing to the absence of a clear explanation for the patient's acute renal failure, renal biopsy was performed 12 days after the onset of symptoms.
Effective ionic dialysance (EID) is an online measure of hemodialysis (HD) effective urea clearance that is calculated using changes in dialysate sodium conductivity. Effective ionic dialysance is blood flow (Q(b)) dependent. The presence of significant (> or =5%) access recirculation (sAR) during dialysis lowers EID at a given Q(b), thereby lowering EID/Q(b). We propose using EID/Q(b) as a useful chairside tool for detection of sAR in arteriovenous fistulae (AVF). Data were collected from 47 patients with AVF (72% men, mean age 49 +/- 11.8 years, duration on dialysis 3.78 +/- 3.4 years, duration of fistula use 3.35 +/- 3.42 years) dialyzed with an high-efficiency dialyzer with a mass transfer area coefficient (KoA) of 1714 ml/min. Effective ionic dialysance were measured at regular intervals by the Gambro Phoenix dialysis system during treatments. The access recirculation (AR) and access blood flow (Q(a)) were measured using the reference standard saline dilution technique (Transonic HD-02 monitor). Among the 323 HD sessions where Q(b), EID, AR, and Q(a) were available, we identified 17 instances of sAR. The performance of EID/Q(b) as indicator of sAR was assessed by a receiver operator characteristic (ROC) curve (Stata version 10.1). The area under the ROC curve was 0.935 (95% confidence interval 0.869-1.000), which demonstrated a sensitivity of 76.5% and specificity of 96.4% at an EID/Q(b) < or =50% with a positive likelihood ratio of 21, negative likelihood ratio of 0.24, positive predictive value of 54.2%, and negative predictive value of 98.7%. We found similar test performance in patients who received HD with dialyzers with smaller surface areas and lower KoAs. The high specificity of EID/Q(b) makes it an excellent yet simple and early chairside indicator of AVF recirculation.
A 70-year-old diabetic male patient with a baseline serum creatinine of 1.4 mg/dL presented with nausea and vomiting. He was diagnosed with metformin-associated lactic acidosis and acute kidney injury. He was managed with continuous veno-venous hemodiafiltration (CVVHDF). By measuring metformin concentration at different time intervals, we calculated the apparent volume of distribution of metformin at 34.7 L. The decline in serum metformin followed single-compartment first-order kinetics with an elimination rate constant of 0.0418/h and a serum half-life of 16.5 h; no metformin rebound was seen after discontinuation of CVVHDF. Using the previously calculated volume of distribution we calculated the expected serum metformin concentration 25 h post CVVHDF to be 3.0-3.7 μg/mL. The measured serum metformin of 3.4 μg/ml fell within the predicted range. During CVVHDF, dialyzer metformin clearance approximates 88.7 % of dialyzer urea clearance and 90.1 % of dialyzer creatinine clearance.
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