Severe type-B lactic acidosis in a patient with bilateral renal Burkitt's lymphoma.

INTRODUCTION: Lactic acidosis (LA) can be categorized as type A, which occurs in the presence of tissue hypoxia, or type B, occurring in the absence of tissue hypoxia. Hematologic malignancies are an uncommon cause of type B LA. CASE PRESENTATION: A 63-year-old man, HIV-negative, with a history of diabetes mellitus, hypothyroidism, and non-alcoholic fatty liver disease (NAFLD), presented to the ED complaining of acute-on-chronic lumbar pain, and was found to have high serum anion gap (AG) LA. The rest of chemistry and infectious workup was within normal limits. Despite bicarbonate therapy and fluid resuscitation, the patient remained with persistent AG metabolic acidosis and increasing lactic acid up to 14.5 mmol/L. An abdominal computerized tomography (CT) revealed multiple bilateral enhancing lesions in the kidneys, as well as gastric wall thickening. Upper gastrointestinal endoscopy with biopsy showed a high-grade Burkitt's lymphoma. Further staging showed bone marrow involvement and extensive abdominal adenopathy. After two cycles of inpatient chemotherapy with dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab), the patient developed multifocal pneumonia complicated by respiratory failure. Following a prolonged ICU stay, after discussion with the family members, a decision of withdrawal of life-sustaining therapy was reached. CONCLUSION: Persistent LA, without identifiable causes of tissue hypoxia, should prompt clinicians to suspect non-hypoxic etiologies, including occult high-grade malignancies. Hematological malignancies constitute an extremely rare cause of type-B LA, carrying a poor prognosis.

Acute interstitial nephritis following treatment with direct-acting antiviral agents in hepatitis C virus-infected patients: A case series.

Hepatitis C virus (HCV) infection has been associated with several extrahepatic adverse clinical outcomes, including an accelerated rate of loss of kidney function in patients with chronic kidney disease (CKD) and an increased mortality in patients with CKD and kidney failure on hemodialysis. Clinical trials using direct-acting antiviral (DAA) agents have uniformly achieved sustained viral response at 12 weeks (SVR12) rates of > 90% in the general population as well as in patients with CKD/kidney failure on hemodialysis. Sofosbuvir is a DAA prodrug that is phosphorylated into the active metabolite GS-461203, with subsequent dephosphorylation into the inactive metabolite GS-331007. The kidneys clear both sofosbuvir and GS-331007, and its use has been associated with worsening kidney function in some studies. In the HCV-TARGET study, patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min at the initiation of sofosbuvir-based therapy had higher rates of deterioration of kidney function compared to patients with higher eGFR [1]. However, based on recent data demonstrating safety in patients with advanced CKD, the US Food and Drug Administration (FDA) approved the use of sofosbuvir-containing regimens in patients with CKD 4/5 (eGFR of less than 30 mL/min/1.73m2) and end-stage renal disease (ESRD) in late 2019. The current report describes 8 HCV-infected patients who developed acute kidney injury (AKI) with biopsy-proven acute interstitial nephritis (AIN) temporally associated with the use of DAAs. The mean age of the group was 61.3 (± 6 years). The most common HCV genotype (GT) was 1a (n = 7). The DAA formulations were sofosbuvir/ledipasvir (n = 5), elbasvir/grazoprevir (n = 2), and sofosbuvir/simeprevir (n = 1). All patients achieved an SVR12. The mean serum creatinine at the initiation of DAA treatment was 1.5 mg/dL (± 0.6) and increased to 2.03 mg/dL (± 0.7) by the last day of DAA administration. The kidney biopsies were performed at a mean of 320 days (± 247) after achieving an SVR12, at which point the mean creatinine had increased to 2.3 mg/dL (± 1.4). All patients received a course of high-dose corticosteroids after the diagnosis of AIN was confirmed by biopsy. Serum creatinine levels at 3 and 6 months following the completion of steroid therapy were 2.8 (± 1.2) and 3.1 mg/dL (± 1.5), respectively. Three patients had worsening CKD and progressed to kidney failure requiring hemodialysis. These results are consistent with earlier studies demonstrating the efficacy of the DAAs in HCV-infected CKD patients. Of note, the demonstration of AIN in these patients may explain some of the AKI events reported with the use of DAAs in patients with CKD.

Treatment and management options for the hepatitis C virus infected kidney transplant candidate.

A substantial body of literature has unequivocally established that prevalent hepatitis C virus infection in chronic kidney disease (CKD), end stage renal disease (ESRD) and kidney transplant recipients is associated with a negative impact on patient survival. As a consequence of remarkable work that explained the details of the hepatitis C virus (HCV) genome, a class of drugs referred to as the direct-acting antiviral (DAA) agents were developed that targeted specific key sites in viral replication. Large clinical trials in the HCV-infected general population followed soon after that demonstrated cure rates exceeding 95%. Treatment paradigms have been further refined and expanded to populations of patients that were initially excluded from the large pivotal trials. This includes the CKD and ESRD patients for whom there are now safe and effective DAAs available as well. In this context, the focus of decision making has shifted from initially demonstrating safety and efficacy to now identifying which patient should receive therapy and at what point in their CKD/ESRD journey. The specific issue of timing of treatment is particularly relevant to the HCV-infected ESRD patient who is being considered for kidney transplantation. The option of treating with DAAs prior to the transplant or alternatively delaying therapy and treating in the posttransplant period will be influenced by several factors, including patient preference, the extent of liver injury, the availability of a living or deceased donor, and more recently the option of transplanting a kidney from HCV-positive donor. The latter has been associated with the advantage of shortened waiting times and expansion of the organ donor pool. The optimal timing and choice of therapy will be the result of a decision that has been individualized for each patient as a consequence of a process of clear communication involving the patient, primary care physician, nephrologist, gastroenterologist (GI)/hepatologist, and local transplant center.

Tele-Nephrology: A Feasible Way to Improve Access to Care for Patients with Kidney Disease Who Reside in Underserved Areas.

BACKGROUND: The Miami VA Healthcare System serves veterans in three South Florida counties: Miami-Dade, Broward, and Monroe, with an estimated veteran population of 175,000. To overcome geographical barriers and facilitate the access to nephrology clinics, we implemented provider-patient tele-nephrology using secured videoconferencing. METHODS: A retrospective and descriptive study design was used to evaluate the effect of the tele-nephrology clinic intervention. Multiple clinical indicators were included in the analysis: blood pressure (BP) control, stabilization of the renal function, and electrolyte/metabolic control. One hundred one patients who were evaluated in the clinic between 2013 and 2015 were included in the analysis, and the indicators were collected retrospectively. RESULTS: One hundred one patients were included in the analysis, with 95% of patients being male (n = 96) and 5% female (n = 5). The mean age was 65.5 years. Fifty patients had chronic kidney disease (CKD) stage III (49.5%), 14 patients had CKD stage IV (13%), and 8 patients had CKD stage II (7.9%). A one-way analysis of variance between subjects was conducted and showed that the effect of the tele-nephrology clinic intervention on reducing BP was statistically significant (systolic BP less than 140 p value <0.0001). Renal function stabilized but the creatinine changes over time were not statistically significant (p value: 0.50). Potassium showed a significant improvement in this sample (p value: 0.0076). Phosphorous and bicarbonate did not show a statistically significant improvement (p value 0.79 and 0.91, respectively). CONCLUSION: With the tele-nephrology clinic intervention, we were able to effectively improve BP and stabilize renal function in patients with kidney disease who reside in underserved areas.