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      Renal Impairment in Chronic Hepatitis B: A Review

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          The liver plays a key role in the metabolism of proteins. Liver dysfunction affects many organs because it communicates with the spleen and all digestive organs through the portal vein. Additionally, the kidney is an organ that is closely related to the liver and is involved in liver diseases. Glomerulonephritis is an important extrahepatic manifestation of chronic hepatitis B virus (HBV) infection. Nucleos(t)ide analog (NA) therapy effectively suppresses HBV replication by inhibiting HBV polymerase, thus decreasing the levels of serum HBV-DNA and delaying the progression of cirrhosis. Although NA therapy is recommended for all patients with chronic HBV infection, regardless of the level of renal dysfunction, there is limited information on NA use in patients with chronic kidney disease. In addition, in patients with end-stage liver cirrhosis, hepatorenal syndrome can be fatal. Hence, we should take into account the stage of impaired renal function in patients with cirrhosis. The aims of this article are to review the epidemiology, clinical presentation, treatment, and prevention of HBV-associated nephropathy.

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          Most cited references 36

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          Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis.

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            Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study.

            Hepatorenal syndrome is common in patients with advanced cirrhosis and constitutes a major problem in liver transplantation. There is no effective medical treatment for hepatorenal syndrome. Forty-six patients with cirrhosis and hepatorenal syndrome, hospitalized in a tertiary care center, were randomly assigned to receive either terlipressin (1-2 mg/4 hour, intravenously), a vasopressin analogue, and albumin (1 g/kg followed by 20-40 g/day) (n = 23) or albumin alone (n = 23) for a maximum of 15 days. Primary outcomes were improvement of renal function and survival at 3 months. Improvement of renal function occurred in 10 patients (43.5%) treated with terlipressin and albumin compared with 2 patients (8.7%) treated with albumin alone (P = .017). Independent predictive factors of improvement of renal function were baseline urine volume, serum creatinine and leukocyte count, and treatment with terlipressin and albumin. Survival at 3 months was not significantly different between the 2 groups (terlipressin and albumin: 27% vs albumin 19%, P = .7). Independent predictive factors of 3-month survival were baseline model for end-stage liver disease score and improvement of renal function. Cardiovascular complications occurred in 4 patients treated with albumin alone and in 10 patients treated with terlipressin and albumin, yet permanent terlipressin withdrawal was required in only 3 cases. As compared with albumin, treatment with terlipressin and albumin is effective in improving renal function in patients with cirrhosis and hepatorenal syndrome. Further studies with large sample sizes should be performed to test whether the improvement of renal function translates into a survival benefit.
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              Urinary interleukin-18 is a marker of human acute tubular necrosis.

              Interleukin-18 (IL-18) is a mediator of ischemic acute tubular necrosis (ATN) in mice. IL-18 was measured in human urine to determine whether it might serve as a marker of ATN. Seventy-two patients, including healthy controls, patients with different forms of acute renal failure, and patients with other renal diseases, were studied. Patients with ATN had significantly greater median urinary IL-18 concentrations than those with all other conditions: patients with ATN, 644 pg/mg creatinine (mean, 814 +/- 151 [SE] pg/mg creatinine; P <0.0001) versus healthy controls, 16 pg/mg creatinine (mean, 23 +/- 9 pg/mg creatinine); patients with prerenal azotemia, 63 pg/mg creatinine (mean, 155 +/- 68 pg/mg creatinine); patients with urinary tract infection, 63 pg/mg creatinine (mean, 149 +/- 110 pg/mg creatinine); those with chronic renal insufficiency, 12 pg/mg creatinine (mean, 84 +/- 45 pg/mg creatinine); and patients with nephrotic syndrome, 34 pg/mg creatinine (mean, 67 +/- 47 pg/mg creatinine). Median urinary IL-18 concentrations measured in the first 24 hours after kidney transplantation were 924 pg/mg creatinine (mean, 1,199 +/- 187 pg/mg creatinine) in patients who received a cadaveric kidney that developed delayed graft function compared with 171 pg/mg creatinine (mean, 367 +/- 102 pg/mg creatinine) in patients who received a cadaveric kidney with prompt graft function and 73 pg/mg creatinine (mean, 176 +/- 107 pg/mg creatinine) in patients who received a kidney with prompt graft function from a living donor (P <0.002). In kidney transplant recipients, lower urinary IL-18 levels were associated with a steeper decline in serum creatinine concentrations postoperative days 0 to 4 (P = 0.009). IL-18 levels are elevated in urine in patients with ATN and delayed graft function compared with other renal diseases. Urinary IL-18 may serve as a marker for proximal tubular injury in ATN. The clinical application of this test may be substantial because it is reliable, inexpensive, and easy to perform.

                Author and article information

                19 June 2018
                June 2018
                : 6
                : 2
                Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; sevendaysinthesun@ (T.S.); naruhiro-kimura@ (N.K.); t-yokoo@ (T.Y.); saka-a@ (A.S.); kenya-k@ (K.K.); atsunori@ (A.T.); atmc@ (M.T.); hiroterukg@ (S.Y.); terais@ (S.T.)
                Author notes
                [* ]Correspondence: hiroteruk@ ; Tel.: +81-25-227-2207
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (



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