Journal of Renal and Hepatic Disorders
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Wnt/β-Catenin Signalling during Liver Metabolism, Chronic Liver Disease and Hepatocarcinogenesis
Get PDFChronic liver diseases (CLDs) are increasing in prevalence and their end-stage complications, namely, cirrhosis, liver failure and hepatocellular carcinoma represent major global challenges. The most common initiators of progressive CLD are viral hepatitis and long-term alcohol abuse as well as steatosis and steatohepatitis. Irrespective of the underlying aetiology, a common feature of CLD is the formation of hepatic ductular reactions, involving the proliferation of liver progenitor cells (LPCs) and their signalling to fibrosis-driving hepatic stellate cells. The Wnt/β-catenin pathway has been found to regulate development, stemness and differentiation, and alterations in its activity have been associated with tumour development. Recent data highlight the role of Wnt/β-catenin signalling in hepatic metabolism, steatosis and cancer, and suggest targeting of this pathway as a promising molecular strategy to potentially inhibit CLD progression and hepatocarcinogenesis
Monitoring the Effects of Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide Switch for Tubulotoxicity in Highly Treatment-Experienced or in Very Sick Individuals Infected with HIV
Get PDFTenofovir disoproxil fumarate (TDF) is a common antiretroviral utilised in the treatment of human immunodeficiency virus (HIV) and hepatitis B infections. It is associated with the development of tubulotoxicity and tubulopathies, and is not recommended in the treatment of patients with baseline chronic kidney disease. Until now, guidelines have suggested frequent monitoring of serum biochemistry to detect the development of such complications. In recent trials, a new prodrug formulation of tenofovir alafenamide (TAF) has been shown to exhibit less tubular toxicity than its counterpart due to a lower serum concentration of its metabolites. In this article, we share our experience with two patients who developed tubulotoxicity following the commencement of TDF-based regimens in HIV, and its improvement following its change to TAF, and review the available literature regarding tenofovir-based nephrotoxicity
An Update on Hepatorenal Syndrome
Get PDFHepatorenal syndrome (HRS) is one of the many potential causes of acute kidney injury (AKI) in patients with decompensated liver disease. HRS is associated with poor prognosis and represents the end-stage of a sequence of reductions in renal perfusion induced by progressively severe hepatic injury. The pathophysiology of HRS is complex with multiple mechanisms interacting simultaneously, although HRS is primarily characterised by renal vasoconstriction. A recently revised diagnostic criteria and management algorithm for AKI has been developed for patients with cirrhosis, allowing physicians to commence treatment promptly. Vasopressor therapy and other general management, such as antibiotic prophylaxis, need to be initiated whilst patients are assessed for eligibility for transplantation. Liver transplantation remains the treatment of choice for HRS but is limited by organ shortage. Other management options, such as transjugular intrahepatic portosystemic shunt, renal replacement therapy and molecular absorbent recirculating system, may provide short-term benefit for patients not responding to medical therapy whilst awaiting transplantation. Clinicians need to be aware of the pathophysiology and management principles of HRS to provide quality care for patients with multi-organ failure
Anaemia of Chronic Kidney Disease: What We Know Now
Get PDFOur understanding of the pathophysiology of the anaemia of chronic kidney disease (CKD) has improved considerably in the last decade with the discovery of the iron regulatory peptide hepcidin. Reduced clearance of hepcidin and the presence of achronic inflammatory state contribute to elevated hepcidin levels in kidney disease. The recent discovery of the various factors and signalling pathways regulating hepcidin has opened up an exciting avenue for research into the development of newer agents that could treat anaemia of CKD. This review highlights our current understanding of iron metabolism in health, the regulators of hepcidin, issues associated with the current available therapies for the treatment of anaemia in CKD and potential novel therapies that could be available in the near future targeting the various factors that regulate hepcidin
Reprogrammed Cell‐based Therapy for Liver Disease: From Labto Clinic
Get PDFA large number of patients are affected by liver dysfunction worldwide. Liver transplantation is the only efficient treatment in a variety of enduring liver disorders including inherent and end-stage liver diseases. The generation of human functional hepato-cytes in high quantities for liver cell therapy is an important goal for ongoing therapies in regenerative medicine. Reprogrammed cells are considered as a promising and unlimited source of hepatocytes, mainly because of their expected lack of immunogenicity and minimized ethical concerns in clinical applications. Despite gained advances in the reprogramming of somatic cells to functional hepatocytes in vitro, production of primary adult hepatocytes that can proliferate in vivo still remains inaccessible. As part of efforts toward translation of cell reprogramming science into clinical practice, more careful cell selection strategies should be integrated into improvement of dedifferentiation and redifferentiation protocols, especially in precision medicine where gene correction is needed. Furthermore, advances in cellular reprogramming highlight the need for developing and evaluating novel standards addressing clinical research interests in this field
Renal Concerns in the Treatment of Chronic Hepatitis B with Tenofovir
Get PDFTenofovir, a third generation oral nucleos(t)ide analogue, currently represents one of the first-line drugs recommended for treating chronic hepatitis B virus (HBV) infection. After oral administration, tenofovir is mostly excreted in the urine by glomerular filtration and proximal tubular secretion. Hence, an impaired kidney function may lead to an increased renal exposure to the drug in patients with coexistent renal damage. This could further worsen kidney disease through different mechanisms of nephrotoxicity such as mitochondrial DNA depletion and tubular cytotoxicity. Despite several studies performed so far to assess tenofovir-related renal toxicity, data in HBV patients are not yet conclusive. Screening of risk factors for kidney disease before starting therapy and a careful monitoring of serum creatinine, glomerular filtration rate, serum phosphate and urine analysis during treatment are advocated to adjust the dose or stop treatment if needed. New biomarkers of tubular injury, such as neutrophil gelatinase associated lipocalin, could become helpful in the future for the timely identification and risk stratification of renal damage induced by tenofovir
Xanthogranulomatous Pyelonephritis: A Rare Presentation
Get PDFXanthogranulomatous pyelonephritis is an uncommon chronic destructive disease process of renal parenchyma, associated with recurrent urinary tract infection. It is seen predominantly in females with no age specificity. The most common symptoms are flank or abdominal pain, fever, palpable mass, and gross hematuria. The common laboratory findings are leukocytosis and anemia. Urine cultures most often reveal Escherichia coli and Proteus mirabilis. Computed tomography is the mainstay of diagnostic imaging for xanthogranulomatous pyelonephritis. Histologically, xanthogranulomatous pyelonephritis presents a granulomatous inflammatory infiltrate mainly composed of lymphocytes, plasma cells, foamy histiocytes, and multinucleated giant cells. The differential diagnosis includes clear cell renal cell carcinoma, sarcomatoid renal cell carcinoma, leiomyosarcoma, malakoplakia, tuberculosis, and interstitial nephritis. Treatment includes antibiotics and surgery. In this article, we report a case of xanthogranulomatous pyelonephritis in a 38-year-old male patient with recurrent urinary tract infection
Liver Transplantation for Monogenic Metabolic Diseases Involvingthe Kidney
Get PDFSeveral metabolic monogenic diseases may be cured by liver transplantation alone (LTA) or by combined liver–kidney transplantation (CLKT) when the metabolic disease has caused end-stage renal disease. Liver transplantation may be regarded as a substitute for an injured liver or as supplying a tissue that may replace a mutant protein. Two groups of diseases should be distinguished. In the first group, the kidney tissue may be severely damaged while the liver tissue is almost normal. In this group, renal transplantation is recommended according to the degree of renal damage and liver transplantation is essential as a genetic therapy for correcting the metabolic disorder. In the second group, the liver parenchymal damage is severe. In this group, liver transplantation is essential to avoid liver failure. LTA may also avoid the progression of the renal disease; otherwise a CLKT is needed. In this review, we describe monogenic metabolic diseases involving the kidney that may have beneficial effects from LTA or CLKT. We also highlight the limitations of such procedures and the choice of alternative medical conservative treatments
Hepatic Venous Outflow Obstruction: Suggestion of a New Classification
Get PDFHepatic venous outflow obstruction (HVOO) is common in developing countries. It is a serious condition that clinically manifests with ascites from sinusoidal hypertension, and carries the risk of high mortality or development of liver cirrhosis. In the past, the eponym Budd–Chiari Syndrome (BCS) was used synonymously for HVOO. In the West, hepatic vein (HV) thrombosis caused by prothrombotic disorders is the main cause of HVOO. In the East, obliterative disease of hepatic portion of inferior vena cava induced by bacterial infection, now renamed hepatic vena cava syndrome, is the common cause of HVOO. These two diseases with different etiology, epidemiology, and natural history are at present grouped together under BCS causing much confusion. Sinusoidal obstruction syndrome, another important cause of HVOO at the level of the sinusoid and terminal HV, was left out in the classification of HVOO. In this article, the pathophysiology of sinusoidal hypertension is described, the term BCS is redefined, and a new classification of HVOO is suggested
Outcomes of Albumin Use in the Treatment of Acute Hepatorenal Disorders: A Single Center Experience
Get PDFoai:jrenhep.com:article/2Intravenous albumin is recommended for hepatorenal disorders (HRD), but individuals who do not recover renal function may beat a high risk for pulmonary edema. We reviewed outcomes by the amount of albumin infused in 93 patients not receiving dialysis at admission but being treated with intravenous albumin for acute HRD at our institution. Absence of renal recovery was defined as no decrease in serum creatinine and requirement of dialysis during hospitalization, and partial renal recovery was defined as a decrease in serum creatinine but not to prehospitalization levels. Associations of clinical factors including total albumin infused, presence of renal recovery, and oliguria with the development of pulmonary edema during hospitalization were determined using logistic regression. Of the 93 patients, 20 patients had complete renal recovery, 17 patients had partial renal recovery, and 56patients showed no renal recovery. Most patients received 300–600 g of albumin. Overall, 47.3% of patients developed pulmonary edema (n=44), but the risk was 75% in patients with oliguria on presentation and no renal recovery versus 17% in those with no oliguria and complete renal recovery (P<0.001). In the logistic regression model, oliguria (3.32; 95% confidence interval [CI]:1.12, 9.81) and no renal recovery (3.38; 95% CI: 1.24, 9.16) were each associated with higher odds of pulmonary edema after adjustment for covariates. No association was noted between total albumin infused and pulmonary edema. In summary, absence of renal recovery and oliguria in patients with HRD receiving intravenous albumin is associated with a higher risk of pulmonary edema