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.

Treating hepatitis C virus in dialysis patients: How, when, and why?

The identification of hepatitis C virus (HCV) occurred in 1989, and soon thereafter, it was recognized that there was a higher prevalence of anti-HCV seropositivity in patients with end-stage renal disease (ESRD) when compared to the general population. Multiple extrahepatic manifestations have been associated with HCV infection in patients with ESRD; these include an increased prevalence and risk of cardiovascular complications, insulin resistance, diabetes mellitus, and lymphoproliferative disorders. Infection with HCV has also been associated with an increased relative risk of mortality in the ESRD patient when contrasted to those patients without infection. The availability of second-generation direct-acting antiviral agents has revolutionized the treatment of HCV in both the general population as well as those patients with advanced chronic kidney disease and receiving dialysis. These new treatment protocols are very well tolerated with limited side effects and manageable drug-drug interactions while achieving remarkable sustained viral response rates. It is important that nephrologists become familiar with the differing strategies available for HCV-infected ESRD patients so that the appropriate decision of when and who to treat can be made for each patient.

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.

Opportunities for treatment of the hepatitis C virus-infected patient with chronic kidney disease.

The prevalence of hepatitis C virus (HCV) infection amongst patients with chronic kidney disease (CKD) and end-stage renal disease exceeds that of the general population. In addition to predisposing to the development of cirrhosis and hepatocellular carcinoma, infection with HCV has been associated with extra-hepatic complications including CKD, proteinuria, glomerulonephritis, cryoglobulinemia, increased cardiovascular risk, insulin resistance, and lymphoma. With these associated morbidities, infection with HCV is not unexpectedly accompanied by an increase in mortality in the general population as well as in patients with kidney disease. Advances in the understanding of the HCV genome have resulted in the development of direct-acting antiviral agents that can achieve much higher sustained virologic response rates than previous interferon-based protocols. The direct acting antivirals have either primarily hepatic or renal metabolism and excretion pathways. This information is particularly relevant when considering treatment in patients with reduced kidney function. In this context, some of these agents are not recommended for use in patients with a glomerular filtration rate < 30 mL/min per 1.73 m2. There are now Food and Drug Administration approved direct acting antiviral agents for the treatment of patients with kidney disease and reduced function. These agents have been demonstrated to be effective with sustained viral response rates comparable to the general population with good safety profiles. A disease that was only recently considered to be very challenging to treat in patients with kidney dysfunction is now curable with these medications.

Transplantation of kidneys from hepatitis C-positive donors into hepatitis C virus-infected recipients followed by early initiation of direct acting antiviral therapy: a single-center retrospective study.

The availability of direct acting antiviral agents (DAA) has transformed the treatment of hepatitis C virus (HCV) infection. The current study is a case series that reports the outcomes from a cohort of twenty-five HCV-infected ESRD patients who received a kidney from an anti-HCV-positive deceased organ donor followed by treatment with DAAs in the early post-transplant period. Time to transplantation and the efficacy of DAA therapy as measured by sustained viral response at 12 weeks were assessed. The median waiting time from original date of activation on the United Network Organ Sharing (UNOS) waiting list until transplantation was 427 days; however, the median time from entering the patient into UNetsm for a HCV-positive offer until transplantation was only 58 days. The 25 patients were started on antiviral treatment early post-transplant (median 125 days) and 24 of 25 (96%) achieved a sustained virologic response at 12 weeks. Tacrolimus dose adjustments were required during antiviral treatment in 13 patients to maintain therapeutic levels. Accepting a kidney from an anti-HCV-positive deceased donor shortened the waiting time for HCV-infected kidney transplant candidates. We recommend that kidneys from anti-HCV-positive donors should be considered for transplant into HCV-infected recipients followed by early post-transplant treatment with DAA agents.

Hepatitis C Virus Infection in Chronic Kidney Disease.

Soon after the hepatitis C virus (HCV) was identified in 1989, it was recognized that the prevalence of infection in patients with ESRD far exceeded that in the general population. Infection with HCV predisposes to the hepatic complications of cirrhosis and hepatocellular carcinoma. However, important extrahepatic manifestations include immune complex glomerular disease, accelerated progression of CKD, increases in cardiovascular event risk, and lymphoproliferative disorders. Advances in understanding the molecular biology of HCV have ushered in a new era in the treatment of this infection. Second generation direct-acting antiviral agents have revolutionized therapy, with sustained virologic response rates (undetectable viral load 12 weeks after completing therapy) of >90% in most patients. Studies using direct-acting antivirals in patients with CKD and those on dialysis are showing excellent safety and efficacy as well. In this context, it is imperative that nephrologists become familiar with this literature, reviewed here, so that the important decisions, including which patients should be treated and the optimal timing to initiate therapy, are vetted in association with the compounding issues of CKD, ESRD, and kidney transplantation.

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.

Epicardial cardiac rhythm devices for dialysis patients: minimizing the risk of infection and preserving central veins.

Transvenous leads of cardiac rhythm devices (CRDs) are known to cause central stenosis and are vulnerable to contamination during hemodialysis access-related bacteremia. In this retrospective study, nine consecutive chronic hemodialysis patients with transvenous CRD infection due to dialysis access-related bacteremia and recurrent central stenosis are presented. Four patients with tunneled hemodialysis catheters (TDCs) and three with arteriovenous grafts experienced access-related bacteremia that spread to the transvenous CRD. Two patients required repeated angioplasty procedures (less than 3 months apart) for central venous stenosis. Transvenous CRD was removed and replaced with an epicardial system in all. One patient with TDC switched to peritoneal dialysis and did not experience infection of the epicardial system despite two episodes of peritonitis. The remaining TDC (n=3) and graft patients (n=3) received a new TDC after the resolution of bacteremia. While all six experienced on average 1.5 episodes of catheter-related bacteremia (average follow-up = 14.5 months), none developed infection of the epicardial system. The patients with central stenosis have required only one angioplasty each for the past 8 and 6 months. To the best of our knowledge this is the first study to suggest that an epicardial approach might be a preferred method over transvenous leads for chronic hemodialysis patients.

Recurrence of lupus nephritis after kidney transplantation.

The frequency and outcome of recurrent lupus nephritis (RLN) among recipients of a kidney allograft vary among single-center reports. From the United Network for Organ Sharing files, we estimated the period prevalence and predictors of RLN in recipients who received a transplant between 1987 and 2006 and assessed the effects of RLN on allograft failure and recipients' survival. Among 6850 recipients of a kidney allograft with systemic lupus erythematosus, 167 recipients had RLN, 1770 experienced rejection, and 4913 control subjects did not experience rejection. The period prevalence of RLN was 2.44%. Non-Hispanic black race, female gender, and age <33 years each independently increased the odds of RLN. Graft failure occurred in 156 (93%) of those with RLN, 1517 (86%) of those with rejection, and 923 (19%) of control subjects without rejection. Although recipients with RLN had a fourfold greater risk for graft failure compared with control subjects without rejection, only 7% of graft failure episodes were attributable to RLN compared and 43% to rejection. During follow-up, 867 (13%) recipients died: 27 (16%) in the RLN group, 313 (18%) in the rejection group, and 527 (11%) in the control group. In summary, severe RLN is uncommon in recipients of a kidney allograft, but black recipients, female recipient, and younger recipients are at increased risk. Although RLN significantly increases the risk for graft failure, it contributes far less than rejection to its overall incidence; therefore, these findings should not keep patients with lupus from seeking a kidney transplant.

Accuracy of ultrasound in the detection of inflow stenosis of arteriovenous fistulae: results of a prospective study.

While vascular ultrasound (US) has been highlighted to detect vascular access stenosis, its accuracy in the identification of inflow stenosis (IS) (anastomosis and/or juxta-anastomotic area) compared with the gold standard (angiography) has not been evaluated. One hundred three consecutive fistulae referred for interventions were included in this study. Preprocedure US of inflow segment was performed. Angiography from the feeding artery to the right atrium was then conducted. US comparison to angiography in the detection of IS (anastomosis and/or juxta-anastomotic area) was evaluated. Additionally, comparison of US to angiography in the assessment of juxta-anastomotic and anastomotic stenosis was reported separately. Data from 103 patients were available for analysis. Overall, US was negative for IS in 52 cases. Of these, 47 did not show a lesion on angiography. Only five cases demonstrated a stenosis on angiography. Fifty-one cases had IS by US, 50 were confirmed by angiography while one case did not show a lesion on angiography. Consequently, US had a sensitivity of 91%, specificity of 98%, and positive and negative predictive values were 98% and 90%, respectively. The sensitivity, specificity, negative, and positive predictive values for juxta-anastomotic and anastomotic lesions evaluated separately were 92%, 98%, 92%, 98% and 79%, 100%, 95%, 100%, respectively. Linear regression analysis showed a significant positive correlation between US and angiography for anastomotic (r2=0.71, p<0.0001; slope=0.63+/-0.098 and intercept=24+/-6) and juxta-anastomotic stenosis (r2=0.71, p<0.0001; slope=0.68+/-0.060 and intercept=23+/-4). These results reveal that US has a high degree of accuracy in the detection of IS.

Renovascular and renoprotective properties of telmisartan: clinical utility.

Chronic kidney disease (CKD) affects approximately 26 million adults in the United States and millions of others are at increased risk. Type 2 diabetes and hypertension are the two main causes of CKD. Blood pressure control is critical to slow the progression of CKD. Despite adequate control, however, patients continue to progress to end-stage renal disease. Angiotensin receptor blockers (ARBs) are commonly used in the management of hypertension and CKD and have been shown to exert renoprotective effects that are in addition to, but independent of, blood pressure lowering. Telmisartan is a long-acting ARB with pharmacological properties beyond blockade of the angiotensin II type 1 receptor, including activation of the peroxisome proliferator activated receptor-γ (PPAR-γ). This article reviews the beneficial renal and vascular protective effects of telmisartan.

Existe evidencia para el inicio de terapias renales sustitutivas a niveles de filtrado glomerular elevado?: [revisión] / Is there evidence for an early start on renal replacement therapy in patients with higher glomerular filtration rate?: [review]

En los Estados Unidos se está notando un incremento del inicio precoz de terapias renales sustitutivas en esta última década. Del 19% de pacientes que iniciaron diálisis con filtrado glomerular por encima de 10 ml/min/1,73m2 en 1996 se ha pasado a un 45%. La presente revisión pretende hacer hincapié en este fenómeno, presentado evidencia referente a ello. No se conocesi existe beneficio alguno para el comienzo precoz de diálisis. Los datos demuestran un incremento de la mortalidad en diálisis precoz que no parece ser debido a las morbilidades de los pacientes con insuficiencia renal crónica terminal. La función renal residual se puede afectar durante la diálisis de inicio comprometiendo la supervivencia del paciente a largo plazo. Finalmente, se expone el posible gasto financiero que esta tendencia acarrea a nuestro sistema de salud. Son necesarios estudios clínicos aleatorizados que den respuestas a estos dilemas...

There is a trend in the last decade for an increase in early initiation in renal replacement therapy in the United States. In 1996 19% of patients initiated dialysis with an estimated glomerular filtration over 10 ml/min/1.73m2 percentage that actually has increase to 45%. This review will show the reasons and evidence behind the current tendencies. There is no factual evidence to support the claim of the beneficial effects in early dialysis starts. Data so far shows increase mortality in early dialysis, unrelated to the co-morbidities of patients with advanced chronic kidney disease. Residual renal function could also be affected by early initiation of dialysis, hampering survival in the long run. Finally will be showing the financial burden to the health system. Randomized clinical trials are needed to answer these questions...