Hepatitis C virus-related cryoglobulinemic glomerulonephritis: long-term remission after antiviral therapy

BACKGROUND: Renal involvement in patients with hepatitis C virus (HCV) infection commonly manifests as cryoglobulinemic glomerulonephritis (CGN). The combination of interferon-alpha (IFN-alpha) and ribavirin, which is currently considered the standard antiviral therapy in chronic hepatitis C, could be difficult to carry out in cryoglobulinemic patients who are frequently anemic, even in the absence of renal failure. Clinical and histologic long-term results of this therapeutic regimen have not been so far reported in patients with CGN. METHODS: Three patients with HCV-related CGN and slightly impaired kidney function were treated with IFN-alpha and ribavirin for 12 months, and subsequently were followed up for 24 to 36 months. Two of these patients who were anemic were pretreated with erythropoietin (EPO). In each patient renal biopsy was performed before starting therapy and repeated 14 to 26 months after the end of treatment. RESULTS: In all three patients, antiviral therapy induced sustained virologic response, which was followed by clear improvement in clinical, biochemical, immunologic, and histologic features. Clinical and biochemical improvement steadily progressed in all three patients, achieving normal or nearly normal results at the end of follow-up. In contrast, some immunologic features, such as serum levels of C4 and rheumatoid factor activity, did not normalize in two and three patients, respectively. Posttreatment renal biopsies showed mildly active histologic lesions. CONCLUSION: Antiviral therapy with IFN-alpha and ribavirin may be considerably beneficial in patients with HCV-related CGN who obtain sustained virologic response.     

Horseshoe kidney transplantation: an overview

The horseshoe kidney is the most common anatomical renal variation. It represents a fusion anomaly, mainly at the lower poles, occurring between the 4th and 6th week of gestation. Horseshoe kidneys display a great variation in origin, number and size of the vasculature. Transplantation of these deviant kidneys can be done en bloc or they can be split into two halves and transplanted into two recipients, depending on the number of vessels and the anatomy of the urinary collecting system. A literature review reveals 31 case histories, published between 1975 and 1998. Of these 21 were transplanted into 38 recipients after division and ten were implanted en bloc. Nineteen grafts (41%) showed immediate function and 21 grafts (46%) showed delayed function. Thrombosis and acute rejection, leading to non-function was seen in six grafts (13%). The overall success rate was 87%) with a mean follow-up of 22 months. The results of horseshoe kidney transplantation are good. provided that attention is paid to certain technical details. Because of donor scarcity, horseshoe kidneys should be used for transplantation.     

Hepatitis C virus-related acute and chronic hepatitis in hemodialysis patients.

The incidence of HCV antibodies has been evaluated in 123 chronic hemodialysis (HD) patients (Group A; 55 M and 68 F) and in 37 consecutive HD patients (group B) admitted to our hospitals for acute hepatitis. In group A, HCV antibodies were present in 27% of the patients. 20 of 36 (55%) had previously received blood transfusions. 21 patients (58%) were also positive for HBV Ab. In 8 patients, ALT were significantly increased. In group B, the diagnosis of HCV-related acute hepatitis was made in 11 patients. 8 of them had previously received blood transfusions. Seroconversion occurred 2-3 months after onset of the disease.     

Hepatitis C infection in kidney transplantation

Liver disease is an important cause of morbidity and mortality among solid organ transplant recipients. Twenty-five percent of long-term survivors after kidney transplantation will die because of liver failure. Hepatitis C (HCV) and hepatitis B (HBV) infection are by far the most significant causes of chronic liver disease in this patient population. A comprehensive review is provided dealing with the clinical impact of HCV infection in different scenarios such as: hemodialisis, acute infection in kidney transplant patients, and the debated policy of performing kidney transplantation from HCV-positive kidney donors in positive recipients. Some related conditions such as diabetes and kidney-related HCV are discussed. Finally, an approach as well as a treatment proposal is provided by the authors.     

Hepatitis C virus infection and kidney transplantation

Hepatitis C virus (HCV) infection is an important problem in the patient with end-stage renal disease. After transplantation, liver disease is more frequent in HCV-positive patients than in HCV-negative patients. In the long run, this leads to important liver complications. The patients have a higher risk for developing proteinuria and infections. Long-term patient and graft survival rates are lower in HCV-positive patients than in HCV-negative graft recipients. Mortality is higher, mainly as a result of liver disease and infections. Despite this, transplantation is the best option for the HCV-positive patient with end-stage renal disease. Transplantation of HCV-positive kidneys should be offered to HCV-positive recipients in whom HCV RNA is detected in the serum. Finally, several measures after transplantation minimize the consequences of HCV infection. Adjustment of immunosuppression and careful follow-up in the outpatient clinic for early detection of proteinuria, infection, or worsening of liver disease are mandatory.     

Hepatitis C virus-related fibrosing cholestatic hepatitis after cardiac transplantation: is azathioprine a contributory factor?

We report a patient who acquired hepatitis C virus (HCV) infection at cardiac transplantation, developing fibrosing cholestatic hepatitis (FCH) with early liver failure and a fatal outcome. FCH is a recently described clinicopathological entity characterized by a cholestatic pattern of serum liver enzyme abnormalities, a progressive course leading to liver failure, and a pathological picture defined by periportal fibrosis, neutrophilic infiltrates and signs of histological cholestasis. Although it was initially described secondary to hepatitis B virus infection, it has also been recently related to HCV infection. Some histopathological features consistent with azathioprine hepatotoxicity like cholestasis, perisinusoidal fibrosis, veno-subocclusive lesions and nodular regenerative hyperplasia were also observed in this case. Therefore, a direct cytopathic effect of HCV and the concurrent pathogenic role of azathioprine hepatotoxicity may be involved in the development of this complication of transplantation.     

Hepatitis C virus infection in end‐stage renal disease and kidney transplantation

Liver disease secondary to chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in patients with end‐stage renal disease (ESRD) on renal replacement therapy and after kidney transplantation (KT). Hemodialytic treatment (HD) for ESRD constitutes a risk factor for bloodborne infections because of prolonged vascular access and the potential for exposure to infected patients and contaminated equipment. Evaluation of HCV‐positive/ESRD and HCV‐positive/KT patients is warranted to determine the stage of disease and the appropriateness of antiviral therapy, despite such treatment is challenging especially due to tolerability issues. Antiviral treatment with interferon (IFN) is contraindicated after transplantation due to the risk of rejection, and therefore, treatment is recommended before KT. Newer treatment strategies of direct‐acting antiviral agents in combination are revolutionizing HCV therapy, as a result of encouraging outcomes streaming from recent studies which report increased sustained viral response, low or no resistance, and good safety profiles, including preservation of renal function. KT has been demonstrated to yield better outcomes with respect to remaining on HD although survival after KT is penalized by the presence of HCV infection with respect to HCV‐negative transplant recipients. Therefore, an appropriate, comprehensive, easily applicable set of clinical practice management guidelines is necessary in both ESRD and KT patients with HCV infection and HCV‐related liver disease.     

Heavy chain deposition disease: an overview

Heavy chain deposition disease (HCDD) is one of three entities of monoclonal immunoglobulin deposition disease, characterized histopathologically by the presence of nodular glomerulosclerosis and glomerular and tubular deposition of monoclonal heavy chains without associated light chains. Although HCDD is an extremely rare disease, >30 cases have been reported to date in the literature. Of these cases, only three cases have been reported in Japan. The majority of the patients presents with nephrotic syndrome, hematuria, and hypertension, and develop progressive renal failure with or without the complication of multiple myeloma. Some cases have been treated successfully using chemotherapy. Because of its rarity, a thorough understanding of HCDD is essential for both accurate diagnosis and adequate subsequent treatment.     

Ambulatory blood pressure measurement in kidney transplantation: an overview

Adequate control of hypertension is among the most important aims of medical management of the kidney transplant recipient, with the aim of reducing the risk of premature cardiovascular disease and preserving graft function. Antihypertensive therapy should be adjusted according to the best available estimates of usual resting blood pressure. If clinic measurements are used, care should be taken to ensure that these measurements are taken under optimal conditions. Home blood pressure monitoring is a useful adjunct in many patients. Ambulatory blood pressure monitoring gives valuable additional data; mean ambulatory blood pressure correlates better with markers of target organ damage such as left ventricular hypertrophy. However, current treatment thresholds and targets are based on clinic measurements. Ambulatory blood pressure monitoring is certainly a useful adjunct to clinic and home blood pressure measurement, but its role in routine clinical practice in the transplant clinic remains to be defined.     

Hepatitis A virus-related late-onset hepatic failure: a case report

Late-onset hepatic failure, the least of the fulminant hepatic failures, has not occurred in patients with hepatitis A virus-related acute liver failure. We report a rare case of hepatitis A virus-related late-onset hepatic failure treated successfully by an emergent liver transplant. A 58-year-old Japanese woman who presented with fever and general malaise was diagnosed as having jaundice and liver dysfunction by a positive serum test for anti-hepatitis A virus IgM, which ultimately led to a diagnosis of acute hepatitis A virus associated hepatitis. Despite intensive treatment, her general condition was poor, and she developed a hepatic coma 79 days from the onset of the disease. Under a diagnosis of hepatitis A virus-related late onset hepatic failure, she was given a living-donor liver transplant 82 days from the start of the disease. The resected native liver revealed submassive necrosis with marked cholestasis, compatible with late-onset hepatic failure. Today, 5 years after the transplant, she is alive and well with no signs of recurrent hepatitis A virus-hepatitis. This case should alert the physician to the clinical management of a patient with hepatitis A virus-related acute liver failure.     

Hepatitis C virus, an important risk factor for tuberculosis in immunocompromised: experience with kidney transplantation

Little is known about the role of hepatitis C virus (HCV) infection in the development of tuberculosis (TB) in patients with immunosuppression. We performed a retrospective case–control study (1:4) to investigate by univariate and multivariate logistic regression analysis the importance of HCV infection in the development of TB in a cohort of kidney transplant recipients (KTR). TB was diagnosed in 16 out of 2012 (0.8%) KTR between 1976 and 2004. The percentage of HCV-positive patients was significantly higher in cases than in controls (56.3% vs. 18.8%; P  = 0.02). By multivariate analysis, the only two independent risk factors associated with the development of TB were the presence of HCV infection ( P  = 0.003; OR = 6.5; 95% CI 1.9–23) and serum creatinine over 1.5 mg/dl ( P  = 0.03; OR = 4.8; 95% CI 1.1–21). HCV infection and chronic graft dysfunction are important risks factors for TB in KTR.     

Hepatitis B in chronic kidney disease: moving toward effective prevention

Control of hepatitis B virus (HBV) infection has been a continuous challenge in the management of patients with advanced kidney disease. HBV infections are still difficult to treat, so the main objective is disease prevention by timely immunization with hepatitis B surface antigen vaccines. In the general population, a simple two- or three-standard-dose vaccination strategy has been proven to be highly successful. In contrast, an intensified and more tailored approach is evolving in patients with advanced renal failure.     

Adynamic bone disease: an update and overview

Adynamic bone disease (ABD) is a variety of renal osteodystrophy characterized by reduced osteblasts and osteoclasts, no accumulation of osteoid and markedly low bone turnover. It has been found in a relatively high percentage of patients on dialysis, either peritoneal or hemodialysis, but also in CKD patients on conservative treatment. The histologic pattern of ABD is generally associated to low levels of PTH. However, PTH serum levels in CKD are generally higher than normal even when associated to ABD. Therefore, it is felt that, basically in uremia, bone tissue is resistant to PTH, so that a relative reduction of its levels is able to induce the emergence of a low turnover state. Several factors theoretically responsible for skeletal resistance to PTH, and able to slow bone turnover have been considered. Among these are downregulation of PTH receptors in bone cells, increased levels of osteoprotegerin, decreased production and circulating levels of bone morphogenetic proteins, the peripheral effect of leptin and also a possible effect of increased N-terminal truncated PTH molecular species, which have been found to counteract the whole molecule, PTH 1-84 on the bone. In conclusion, ABD should probably be considered a skeletal condition induced by overtreatment of secondary hyperparathyroidism and not a disease. However, its development reveals a deranged ability of uremic bone to maintain a normal bone turnover, when PTH serum levels decrease beyond relatively low levels, which would be considered normal in the general population.