Independent risk factors for chronic cyclosporine induced nephropathy in children with nephrotic syndrome.

BACKGROUND: Cyclosporine A (CsA) has been widely used in children with steroid dependent and steroid resistant nephrotic syndrome (NS) because of its efficacy in relieving these patients from systemic side effects of steroids. However, its long term use is controversial, since chronic CsA induced nephropathy (CsAN) may develop in a considerable number of patients. AIMS AND METHODS: In order to clarify the risk factors for the development of CsAN, the clinical characteristics of children with steroid dependent or steroid resistant NS taking CsA (target blood trough levels 50-150 ng/ml) for more than six months, managed at a single centre, were retrospectively analysed. RESULTS: Thirteen of 30 children (24 boys and 6 girls) taking CsA (mean duration 43 months, range 6-144) had CsAN defined as the presence of CsA associated arteriopathy with or without striped tubulointerstitial lesions. The multivariate analysis revealed that CsA treatment for more than 36 months and an age younger than 5 years at the start of CsA treatment were independent risk factors for the development of CsAN. The univariate analysis also showed that patients with CsAN had more frequent relapses during CsA treatment than those without CsAN. CONCLUSION: An alternative treatment should be seriously considered after a 36 month administration of CsA in order to prevent CsAN. Data also suggest that CsA treatment in children younger than 5 years should be avoided if possible.     

Independent risk factors for chronic cyclosporine induced nephropathy in children with nephrotic syndrome

Background

Cyclosporine A (CsA) has been widely used in children with steroid dependent and steroid resistant nephrotic syndrome (NS) because of its efficacy in relieving these patients from systemic side effects of steroids. However, its long term use is controversial, since chronic CsA induced nephropathy (CsAN) may develop in a considerable number of patients.

Aims and Methods

In order to clarify the risk factors for the development of CsAN, the clinical characteristics of children with steroid dependent or steroid resistant NS taking CsA (target blood trough levels 50–150 ng/ml) for more than six months, managed at a single centre, were retrospectively analysed.

Results

Thirteen of 30 children (24 boys and 6 girls) taking CsA (mean duration 43 months, range 6–144) had CsAN defined as the presence of CsA associated arteriopathy with or without striped tubulointerstitial lesions. The multivariate analysis revealed that CsA treatment for more than 36 months and an age younger than 5 years at the start of CsA treatment were independent risk factors for the development of CsAN. The univariate analysis also showed that patients with CsAN had more frequent relapses during CsA treatment than those without CsAN.

Conclusion

An alternative treatment should be seriously considered after a 36 month administration of CsA in order to prevent CsAN. Data also suggest that CsA treatment in children younger than 5 years should be avoided if possible.     

环孢霉素A与他克莫司治疗儿童难治性肾病综合征疗效及安全性对照研究

目的 评估环孢霉素A与他克莫司治疗儿童难治性肾病综合征的疗效及安全性。方法 回顾性分析2012年6月至2018年6月在上海市儿童医院接受环孢霉素A与他克莫司治疗的118例难治性肾病综合征患儿信息，包含患儿一般情况、实验室检查、肾组织病理、治疗后转归及不良反应等，并进行统计分析。采用Kaplan-Meier生存分析绘制生存曲线，行相关比较分析。结果 一般临床资料：纳入环孢霉素A治疗病例总计66例，其中18例为激素耐药型肾病综合征，45例为激素依赖型肾病综合征，3例为频反复型肾病综合征，其中56例行肾穿刺活检。52例他克莫司组中12例为激素耐药型肾病综合征，40例为激素依赖型肾病综合征，其中47例行肾穿刺活检；疗效及安全性分析：环孢霉素A与他克莫司对难治性肾病综合征维持远期完全缓解无组间差异。但治疗第6个月，难治性肾病综合征他克莫司组完全缓解率（86.5%）明显高于环孢霉素A组（68.2%），差异有统计学意义（P<0.05），其中以激素依赖型/频反复型肾病综合征疗效差异有统计学意义（P<0.05），激素耐药型肾病综合征组间疗效无统计学差异。此外，在微小病变组及非微小病变组内，环孢霉素A与他克莫司无疗效差异；副反应方面，他克莫司组多毛症发生率、牙龈增生发生率均明显低于环孢霉素A组，且有显著性差异（P<0.01），但在使用他克莫司第16个月及18个月后出现2例急性胰腺炎患儿。环孢霉素A组急性肾损伤（5/66）及慢性肾毒性改变（2/66）发生率高于他克莫司组。结论 环孢霉素A与他克莫司对难治性肾病综合征远期疗效无差异。对于激素依赖型/频反复型肾病综合征患儿，他克莫司短期疗效较环孢霉素A更好，但需警惕急性胰腺炎发生。对环孢霉素A累计治疗时间超过30个月患儿需高度警惕钙调神经磷酸酶抑制剂肾毒性发生。     

Pharmacodynamic monitoring of cyclosporine A by NFAT‐regulated gene expression and the relationship with infectious complications in pediatric renal transplant recipients

Billing H, Giese T, Sommerer C, Zeier M, Feneberg R, Meuer S, Tönshoff B. Pharmacodynamic monitoring of cyclosporine A by NFAT‐regulated gene expression and the relationship with infectious complications in pediatric renal transplant recipients.
Pediatr Transplantation 2010: 14:844–851. © 2010 John Wiley & Sons A/S. Abstract: Pharmacokinetic monitoring of CsA is unsatisfactory, because at comparable CsA blood concentrations, the frequency and severity of adverse effects vary considerably among patients. We have therefore recently developed a precise, reliable, and robust whole‐blood pharmacodynamic assay that measures the suppression of CsA‐target genes in T lymphocytes. Because of the different characteristics of CsA pharmacokinetics in children and the higher propensity for infectious complications, this assay requires validation in the pediatric patient population. We therefore quantified in a prospective study of 45 pediatric renal transplant recipients the residual expression of NFAT‐regulated genes in lymphocytes by RT‐PCR and correlated these findings with the frequency of recurrent infections in the maintenance period post‐transplant. Patients with recurrent infections showed a significantly stronger inhibition of NFAT‐regulated gene expression (18.2%) than patients without recurrent infections (31.7%; p = 0.012). This difference was specific, because various PK parameters of CsA and the concomitant immunosuppressive therapy were comparable between patients. Multivariate regression analysis showed that patient age and residual NFAT‐regulated gene expression were the only independent determinants of recurrent infections. By ROC curve analysis, a cutoff value of 23% residual NFAT‐regulated gene expression had the highest sensitivity (71.1%) and specificity (65.4%) for the discrimination of patients with and without recurrent infections. Pharmacodynamic monitoring of CsA by measurement of residual NFAT‐regulated gene expression in T lymphocytes has the potential to identify over‐immunosuppressed pediatric renal transplant recipients and is therefore a useful tool for the optimization of CsA therapy.     

长疗程环孢素A治疗儿童激素耐药型肾病综合征的疗效和预后

目的 观察激素耐药的儿童肾病综合征(SRNS)应用环孢素A(CsA)长疗程治疗的疗效并分析影响疗效的相关因素.方法 回顾性分析疗程2年的CsA治疗SRNS病例20例,男:女为3:1;平均年龄5.5岁,肾病病理类型微小病变(MCNS)15例,局灶节段肾小球硬化(FSGS)4例,系膜增生性肾炎(MsPGN)1例.结果 (1)完全缓解13例(65%),部分缓解4例(20%),CsA无效3例(15%),总有效率85%.平均随访时间40.5个月,复发率45%.(2)CsA治疗微小病变肾病的有效率为93%,非微小病变为60%,但两者差异无统计学意义.(3)毒副作用:多毛、齿龈增生和高血压的发生率分别为75%、25%和10%,2例出现可逆性的肾损伤,4例出现尿NAG/Cr增高,神经系统症状2例.3例重复肾活检未发现CsA相关的肾小管间质纤维化病变.结论 对儿童激素耐药型肾病综合征CsA长疗程治疗有良好的疗效.小剂量CsA长期治疗未发现药物相关的肾小管间质纤维化和肾功能损伤.CsA长期治疗的安全性和预后有待进一步研究.     

Liver disease in transfusion dependent thalassaemia major.

AIMS: To study the prevalence and severity of liver diseases of transfusion dependent thalassaemia major patients, and correlate the histological and biochemical changes of iron overload in liver with the peripheral blood markers. METHOD: Liver biopsy was performed to assess the histological changes and liver iron content (LIC). RESULTS: One hundred patients were evaluated (median age 11.7 years, range 1.5-27). A total of 81 liver biopsies were performed in 73 patients; 43 samples were analysed for LIC. Grade 3-4 haemosiderosis and hepatic fibrosis was found in 44% and 30% of patients respectively; both were significantly associated with higher serum ferritin, liver enzymes, and LIC. Very high LIC (>15 mg/g dry weight) was present in 16.3% of patients. CONCLUSION: Severe haemosiderosis and hepatic fibrosis were common in patients with thalassaemia major despite the use of chelation therapy. Liver biopsy provided information on fibrosis and LIC which could not be accurately predicted from peripheral blood markers.     

Liver disease in transfusion dependent thalassaemia major

Aims: To study the prevalence and severity of liver diseases of transfusion dependent thalassaemia major patients, and correlate the histological and biochemical changes of iron overload in liver with the peripheral blood markers. Method: Liver biopsy was performed to assess the histological changes and liver iron content (LIC). Results: One hundred patients were evaluated (median age 11.7 years, range 1.5–27). A total of 81 liver biopsies were performed in 73 patients; 43 samples were analysed for LIC. Grade 3–4 haemosiderosis and hepatic fibrosis was found in 44% and 30% of patients respectively; both were significantly associated with higher serum ferritin, liver enzymes, and LIC. Very high LIC (>15 mg/g dry weight) was present in 16.3% of patients. Conclusion: Severe haemosiderosis and hepatic fibrosis were common in patients with thalassaemia major despite the use of chelation therapy. Liver biopsy provided information on fibrosis and LIC which could not be accurately predicted from peripheral blood markers.     

Practice recommendations for the monitoring of renal function in pediatric non‐renal organ transplant recipients

The management of non‐renal pediatric solid organ transplant recipients has become complex over the last decade with innovations in immunosuppression and surgical techniques. Post‐transplantation follow‐up is essential to ensure that children have functioning allografts for as long as possible. CKD is highly prevalent in these patients, often under recognized, and has a profound impact on patient survival. These practice recommendations focus on the early detection and management of hypertension, proteinuria, and renal dysfunction in non‐renal pediatric solid organ transplant recipients. We present seven practice recommendations. Renal function should be monitored regularly in organ transplant recipients, utilizing assessment of serum creatinine and cystatin C. GFR should be calculated using the new Schwartz formula. Transplant physicians should also monitor blood pressure using automated oscillometric devices and confirm repeated abnormal measures with manual blood pressure readings and ambulatory 24‐h blood pressure monitoring. Proteinuria and microalbuminuria should also be assessed regularly. Referrals to a pediatric nephrologist should be made for non‐renal organ transplant recipients with repeated blood pressures >95th percentile using the Fourth Task Force reference intervals, microalbumin/creatinine ratio >32.5 mg/g (3.7 mg/mmol) creatinine on repeated testing and/or GFR <90 mL/min/1.73 m².     

Mycophenolate mofetil promotes prolonged improvement of renal dysfunction after pediatric liver transplantation: experience of a single center

Few studies have evaluated the long-term use of MMF in liver transplanted children with renal dysfunction. The aim of this study is to report the experience of a pediatric transplantation center on the efficacy and security of long-term use of a MMF immunosuppressant protocol with reduced doses of CNIs in stable liver transplanted children with renal dysfunction secondary to prolonged use of CsA or Tac. Between 1988 and 2003, 191 children underwent OLT and 11 patients developed renal dysfunction secondary to CNIs toxicity as evaluated by biochemical renal function parameters. The interval between liver transplantation and the introduction of the protocol varied from one to 12 yr. Renal function was evaluated by biochemical parameters in five phases: immediately prior to MMF administration; 3, 6, 12 and 24 months after the introduction of MMF. Among the patients, nine of them (82%) showed improvement of renal function parameters in comparison with the pretreatment values. The two patients that did not show any improvement were patients in whom the interval of time between OLT and the introduction of MMF was longer. All parameters of liver function remained unchanged. No episodes of acute or chronic rejection or increases in infection rates during the period were detected. Two patients developed transitory diarrhea and leukopenia that were reverted with reduction of MMF dosage. In conclusion, in liver transplanted pediatric patients with CNI-induced chronic renal dysfunction, the administration of MMF in addition to reduced doses of CNIs promotes long-term improvement in renal function parameters with no additional risks.     

Cyclosporine in steroid dependent and resistant childhood nephrotic syndrome

OBJECTIVE: To evaluate the efficacy of cyclosporine (CyA) monotherapy in steroid resistant (SRNS) and steroid dependent (SDNS) nephrotic syndrome in children. DESIGN: A retrospective study. SETTING: Tertiary kidney care center for children at Bangalore. METHODS: Forty-one children with SDNS and SRNS with normal renal functions were treated with CyA at a dose of 6 mg/kg/day initially and maintained at 3 to 4 mg/kg/day if remission was sustained. The dosage was adjusted according to the CyA blood levels in non-responders. RESULTS: The median age of patients was 93 months (range 48-936) months. Thirteen children had minimal change disease (MCNS), 10 had mesangial proliferative glomerulonephritis (GN). Ten had membrano-proliferative (GN) (MPGN) and 8 had focal segmental glomerulosclerosis (FSGS). Median age at onset of disease and median time for CyA usage from disease onset was 22 months and 16 months respectively. Median duration of CyA therapy was 24 months (range 6-72) months. The data was analyzed to determine significance of variables on the outcome. Median follow up was 71 months (range 20-205) months. Eleven children were CyA resistant. Of the remaining 30 who were CyA responders, 22 (73.33%) were CyA dependent. Seven children developed chronic renal failure (CRF). CONCLUSIONS: The predictors for CyA non-responsiveness were steroid resistance, non MCNS on biopsy and longer duration between onset of nephrotic syndrome and CyA usage, irrespective of the age of onset of the disease. There was a higher incidence of CyA dependence among young responders. Patients with CyA resistance are at high risk for significant infections and CRF.     

Acquired renal cysts after pediatric liver transplantation: association with cyclosporine and renal dysfunction

Abstract:  ACKD has been observed in children on dialysis and with chronic renal insufficiency. In one report, ACKD was observed in 30% of pediatric liver transplant recipients after 10 yr. We retrospectively reviewed all renal imaging and measurements of GFR of 235 childhood liver transplant recipients with no known risk for renal cyst formation, no evidence of renal cyst(s) at the time of transplantation and renal imaging at least one yr post-transplant. Twenty-six patients (11%) developed one or more cyst(s). Mean GFR was significantly lower in patients with renal cyst(s). Two (1.4%) of the 146 patients treated with tacrolimus and 24 (27%) of the 89 patients treated with CsA acquired renal cyst(s) (p < 0.001). CsA-treated patients had significantly lower GFR. Multivariate analysis identified CsA as the only independent variable associated with ACKD. These results confirm that ACKD can be a late complication of pediatric liver transplantation. Those at most risk are at least 10-yr post-liver transplantation, have been treated with CsA and have impaired renal function. We speculate that ACKD in these patients is the result of calcineurin inhibitor nephrotoxicity. Whether patients with ACKD will be prone to develop solid renal tumors is unknown.     

High-dose peripheral blood stem cell infusion: a strategy to induce donor-specific hyporesponsiveness to allografts in pediatric renal transplant recipients

We designed and implemented a clinical trial to achieve zero-rejection status in pediatric renal allograft recipients, using granulocyte-macrophage colony-stimulating factor (GM-CSF)-stimulated peripheral blood stem cell (PBSC) infusion. We studied 44 consecutive patients: 24 volunteers in a treated group (Tn) and 20 in a control group (Cn). Both groups were comparable with respect to clinical and laboratory parameters. The Tn group had 70.8% one haplo-match donors and the Cn group had 80% one haplo-match donors. Patients in the Tn group received cyclosporin A (CsA) and 0.4 mg/kg body weight prednisolone as immunosuppressants; azathioprine was added for patients of the Cn group, who received 1 mg/kg body weight prednisolone together with CsA. Living-related donors (LRD) of patients in the Tn group received GM-CSF 450 microg on four consecutive days followed by leucopheresis and immediate transfusion of unmodified PBSC into the recipient. This procedure was repeated once/twice, with one portal and one/two systemic infusions. Our aim was to maximize the dose of PBSC. The total average dose was 22 x 10(8) cells/kg body weight. Lymphocyte cross-match (LCM) was performed before GM-CSF injection and after the last PBSC infusion. Follow-up over an 18-month period revealed 100% graft survival with sustained low serum creatinine (SCr) values in patients of the Tn group as compared with 80% graft survival in patients of the control group who had marginally higher SCr levels. Absence of graft vs. host disease (GvHD), acute rejection episodes, and low incidence of cytomegalovirus (CMV) disease were the principal benefits of this protocol.     

Relation of serum erythropoietin levels to renal excretory function: evidence for lowered set point for erythropoietin production in chronic renal failure

The relationship of serum erythropoietin (Ep) levels to hematocrit and glomerular (GFR) filtration rate was evaluated in patients with chronic renal disease. The Ep level was measured by radioimmunoassay in 119 blood samples from 48 patients obtained over a period of up to 5 years. Hematocrit values correlated significantly with the GFR, but serum Ep levels did not change with a decline in the GFR. Significant anemia was noted only when the GFR fell below 20 ml/min/1.73 m2. Episodes of spontaneous acute hypoxic stress were observed in six patients with chronic renal failure. Serum Ep levels obtained during these episodes (mean +/- SEM: 273 +/- 76 mU/ml) were tenfold higher than Ep levels during stable steady-state chronic renal failure (26 +/- 6 mU/ml), even though Ep levels were inappropriately low for the degree of anemia in the stable state. Our findings suggest that the tissue oxygenation-Ep-hematocrit feedback mechanism operates at a lower set point in patients with chronic renal failure in comparison with normal subjects.     

Prospective evaluation of acute and chronic renal function in children following matched related donor hematopoietic stem cell transplantation

Ileri T, Ertem M, Ozcakar ZB, Ince Unal E, Biyikli Z, Uysal Z, Ekim M, Yalcinkaya F. Prospective evaluation of acute and chronic renal function in children following matched related donor hematopoietic stem cell transplantation.
Pediatr Transplantation 2010: 14: 138–144. © 2009 John Wiley & Sons A/S.
Abstract:  Acute and chronic renal impairment are important complications after HSCT. A prospective study was conducted to investigate the glomerular renal function in children who received allogeneic HSCT from matched related donors. Non-radiation conditioning regimens were used in all but one patient. CrCl and serial measurements of serum creatinine were evaluated prior to HSCT, within the first 100 days and one yr after. AKI was defined as at least a 1.5-fold rise in pre-HSCT serum creatinine within the first 100 days and classified as grade 1 to 3 according to the new definition criteria proposed by "AKI Network." Fifty-seven patients were enrolled in the study and 24 patients (42%) had AKI. CsA, amphotericin B, and SOS were found as risk factors for AKI. One yr after HSCT five patients (10%) had CKD and none of them required dialysis. None of the parameters were found as a predictor for CKD. We conclude that AKI is an important complication of HSCT. Careful monitoring of renal function, minimizing the use of nephrotoxic medication, prophylaxis, and effective treatment of SOS might be effective preventive measures to decrease the incidence of AKI.     

Serum and urinary neutrophil gelatinase‐associated lipocalin levels in children with chronic renal diseases

Background: Recent studies showed that serum and urinary neutrophil gelatinase‐associated lipocalin (NGAL) represents a novel, sensitive, specific biomarker for early detection of acute kidney injury. However, the clinical significance of measuring serum and urinary NGAL on chronic renal diseases remains unclear. Methods: In this study, we measured serum and urinary NGAL levels in patients with several common pediatric renal diseases such as renal dysfunction (estimated glomerular filtration rate < 90 mL/min/1.73 m²), proliferative glomerulonephritis, steroid‐resistant and steroid‐sensitive nephrotic syndrome, and tubular dysfunction. Results: Urinary NGAL level was significantly increased compared with the control in all of these disease groups except in patients with a remission stage of steroid‐sensitive nephrotic syndrome, although a significant increase in serum NGAL level was observed in the renal dysfunction group only. Both serum and urinary NGAL levels showed significant inverse correlations with an estimated glomerular filtration rate in the analysis with total subjects, and also in the analysis with the renal dysfunction group in urinary NGAL. In proteinuric patients, the extent of proteinuria significantly correlated with urinary NGAL level. In patients with tubular dysfunction, the increase of urinary NGAL level was remarkable compared with the other disease groups. Conclusion: These results indicated that urinary NGAL level is a better biomarker for chronic renal diseases in children than serum NGAL level, although multiple pathological mechanisms should be considered in evaluating these NGAL values.     

Bone metabolism and mineral density following renal transplantation.

AIM: To study bone turnover following renal transplantation using a panel of biochemical markers and to correlate the results with both areal and volumetric bone mineral density (BMD). PATIENTS: A total of 31 patients aged 18.1 years were transplanted 5.4 years before this study. Control patients (n = 31) were age and gender matched. METHODS: In addition to measurement of biochemical markers, BMD was measured by single photon absorptiometry and peripheral quantitative computed tomography on the non-dominant radius. RESULTS: Patients had reduced glomerular filtration rate, raised concentrations of serum phosphate, serum procollagene type I carboxy terminal propeptide, osteocalcin, and serum procollagene type I cross linked carboxy terminal telopeptide. The differences were still significant if only patients with normal intact parathyroid hormone were considered. BMD single photon absorptiometry Z score for age was significantly decreased. Following standardisation for height the differences were no longer present. With volumetric techniques patients had normal trabecular but decreased cortical and total BMD compared to age matched controls, but there was no difference from height matched controls. CONCLUSION: Markers of bone turnover are increased following renal transplantation. However, the biochemical analysis did not allow conclusions to be drawn on the bone mineral content. BMD single photon absorptiometry Z score corrected for height and BMD measured by quantitative computed tomography compared to height matched controls were normal in paediatric renal transplantation patients. Height matched controls should be used in both areal and volumetric BMD measurements in states of growth failure.     

Serum immunoglobulin G, M and IgG:IgM ratio as predictors for outcome of childhood nephrotic syndrome

Background  Nephrotic syndrome is an immune mediated disorder of the kidney associated with T cell dysfunction and secondary disturbance of B cell with changes in levels of immunoglobulin and IgG:IgM ratio. These changes in immunoglobulin levels can be used as a proxy marker to understand the clinical variety and prognosis of nephrotic syndrome. Methods  We studied 43 children with nephrotic syndrome during January 2003 to January 2005 in the Pediatric Nephrology Unit, Department of Pediatrics, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Blood samples were collected from the 43 patients, and serum levels of IgG, IgM and IgG:IgM were measured by liquid phase immunoprecipitation assay. Another 20 healthy children attending the laboratory for blood grouping and hepatitis B screening test were enrolled as controls. Results  In the 43 children with nephrotic syndrome, 24 had steroid sensitive nephrotic syndrome (SSNS) and 19 steroid resistant nephrotic syndrome (SRNS). Compared with healthy children, the IgG level was low, IgM level was high, and IgG:IgM ratio was low (P<0.05). The serum IgG level and IgG:IgM ratio were significantly lower in children with SRNS and in children with frequent relapse (FRNS) combined with steroid dependent nephrotic syndrome (SDNS) than in those with infrequent relapse nephrotic syndrome (IFRNS) (P<0.05, respectively). Conclusions  Management of different nephrotic syndromes is based on the levels of immunoglobulins along with clinical and biochemical parameters. The decrease of IgG level as a predictive marker for unfavorable prognosis of nephrotic syndrome in children needs further evaluation in larger scale studies.     

Twenty-four hour monitoring of blood pressure and heart rate in patients with chronic renal failure or renal transplant recipients: Analysis by the cosinor method

Hypertension is a major problem of patients with chronic renal failure or renal transplant recipients. To clarify the characteristics of blood pressure, heart rate, and circadian rhythms of these patients we used an ambulatory blood pressure monitor (ABPM) for 24 h monitoring and analyzed the data by the cosinor method. In eight chronic renal failure patients without dialysis the midline estimating statistic of rhythm (MESOR) of diastolic blood pressure was higher than in controls, but the MESOR of systolic blood pressure was not. Of 11 patients on dialysis some had hypertension and some had hypotension. In 14 renal transplant recipients, especially those with chronic graft rejection, the MESOR of systolic and diastolic pressures were higher than controls, and the increase of blood pressure MESOR had a significant correlation with the elevation of serum creatinine levels. Circadian rhythms of blood pressure were frequently absent in the patients on dialysis, but circadian rhythms of heart rate were not. The use of an ABPM is a non-invasive method to monitor patients and allowed us to know changes of blood pressure and heart rate in the daytime as well as during the night. For the control of hypertension in chronic renal failure, monitoring with an ABPM seems to provide invaluable information.     

Acute Hepatitis B in Children with Papular Acrodermatitis

Thirteen children who had repeated liver biopsies over a period of 2-16 years after the onset of papular acrodermatitis (PAC) were studied retrospectively. Six patients, rebiopsied within 36 months after the onset of PAC, had histologic evidence of chronic periportal hepatitis. However, repeated biopsies in 3 of the patients revealed a normal liver or chronic portal hepatitis. Whereas all patients had at the end of the observation markers of hepatitis B virus infection, 8 of the 10 patients studied had HBs antigenemia. These data indicate that severe active liver disease may regress without treatment in patients who have had PAC. However, the high frequency of a chronic HBsAg-carrier state among these patients suggests either an inefficient clearance of the virus or an altered immune reaction.     

Acute hepatitis B in children with papular acrodermatitis

Thirteen children who had repeated liver biopsies over a period of 2-16 years after the onset of papular acrodermatitis (PAC) were studied retrospectively. Six patients, rebiopsied within 36 months after the onset of PAC, had histologic evidence of chronic periportal hepatitis. However, repeated biopsies in 3 of the patients revealed a normal liver or chronic portal hepatitis. Whereas all patients had at the end of the observation markers of hepatitis B virus infection, 8 of the 10 patients studied had HBs antigenemia. These data indicate that severe active liver disease may regress without treatment in patients who have had PAC. However, the high frequency of a chronic HBsAg-carrier state among these patients suggests either an inefficient clearance of the virus or an altered immune reaction.