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Biomedical subjects

Kar Neng Lai

Publications and source records attributed to Kar Neng Lai.

At least 19 recordsLinked to original sources
PubMed2006

Alleviation of sleep apnea in patients with chronic renal failure by nocturnal cycler-assisted peritoneal dialysis compared with conventional continuous ambulatory peritoneal dialysis.

Nocturnal hemodialysis has been shown to improve sleep apnea in patients who receive conventional hemodialysis. It was hypothesized that nocturnal peritoneal dialysis (NPD) also is effective in correcting sleep apnea in patients who receive continuous ambulatory PD (CAPD). Overnight polysomnography (PSG) was performed in 46 stable NPD and CAPD patients who were matched for demographic and clinical attributes. The prevalence of sleep apnea, defined as an apnea-hypopnea index (AHI; or frequency of apnea and hypopnea per hour of sleep) > or =15, was 52% for NPD patients and 91% for CAPD patients (P = 0.007). The mean (+/-SD) AHI in NPD and CAPD patients was 31.6 +/- 25.6 and 50.9 +/- 26.4 (P = 0.025), respectively. For validation of the efficacy of NPD in alleviating sleep apnea, a fixed sequence intervention study was performed in which 24 incident PD patients underwent one PSG study during mandatory cycler-assisted NPD while awaiting their turn for CAPD training and a second PSG recording shortly after they were established on stable CAPD. The prevalence of sleep apnea was 4.2% during NPD and 33.3% during CAPD (P = 0.016). AHI increased from 3.4 +/- 1.34 during NPD to 14.0 +/- 3.46 during CAPD (P < 0.001). With the use of bioelectrical impedance analysis, total body water content was significantly lower during stable NPD than CAPD (32.8 +/- 7.37 versus 35.1 +/- 7.35 L; P = 0.004). NPD delivered greater reductions in total body water (-2.81 +/- 0.45 versus -1.34 +/- 0.3 L; P = 0.015) and hydration fraction (-3.63 +/- 0.64 versus -0.71 +/- 0.52%; P = 0.005) during sleep. Pulmonary function tests remained unchanged before and after conversion from NPD to CAPD. These findings suggest that NPD may have a therapeutic edge over CAPD in sleep apnea that is associated with renal failure as a result of better fluid clearance during sleep.

Adult↗
PubMed2006

Conversion of ciclosporin A to tacrolimus in kidney transplant recipients with chronic allograft nephropathy.

BACKGROUND: Tacrolimus and ciclosporin might have different effects on intra-renal fibrosis and allograft function in chronic allograft nephropathy (CAN). It is difficult to predict the response to calcineurin inhibitor minimization in patients with CAN. METHODS: This prospective randomized study compared ciclosporin A (CsA)-to-tacrolimus conversion (group A, target tacrolimus trough level 6-8 ng/ml) vs CsA minimization (group B, target CsA trough level 80-100 ng/ml) with regard to efficacy and safety in patients with CAN and deteriorating allograft function. The primary efficacy endpoint was improvement in the slope of inverse serum creatinine (1/SCr) vs time plot. RESULTS: There were 34 evaluable patients (n=16 in group A; n=18 in group B), with similar baseline characteristics. Both groups reached target drug levels after a 3-month run-in period. Over the ensuing 12 months, nine (56.3%) subjects in group A and 10 (55.6%) in group B reached the primary end point (P=0.968). Both groups showed considerable improvement in the slope of 1/SCr vs time plot. There was no significant difference in the slope between groups before and after intervention. Graft survival was 87% in group A and 100% in group B (P=0.121). Acute rejection was encountered in two group A subjects. There was no significant change or difference in blood glucose, lipids, and blood pressure between groups. CONCLUSION: Our results suggest that in patients with CAN and deteriorating allograft function, CsA-to-tacrolimus conversion or CsA minimization achieved comparable efficacies in retarding the decline of graft function. Such contention may be biased by the low patient number. Further studies with a larger cohort are needed for validation.

Adolescent↗
PubMed2006

Activation of tubular epithelial cells in diabetic nephropathy and the role of the peroxisome proliferator-activated receptor-gamma agonist.

The effects of advanced glycation end products (AGE) in the form of glycated albumin (GA) on the proinflammatory phenotype of cultured renal proximal tubular epithelial cells (PTEC) and the therapeutic potential of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist were studied. Human PTEC were exposed to medium alone or supplemented with albumin or GA with or without previous addition of rosiglitazone (0.1 to 0.5 microM). Exposure to GA (up to 0.5 mg/ml) but not the equivalent dose of neat albumin significantly upregulated both mRNA and protein expression of IL-8 and soluble intercellular adhesion molecule-1 (sICAM-1) in a dose- and time-dependent manner. Using immunohistochemistry, ICAM-1 signals were detected in the tubular epithelia and peritubular capillaries in association with AGE deposition and leukocyte infiltration, whereas IL-8 staining was localized in the tubular epithelia of human diabetic kidney biopsies. Also in a dose-dependent manner, GA (0.5 mg/ml) but not albumin caused nuclear translocation of NF-kappaB and activation of mitogen-activated protein kinase (MAPK) p44/p42 and signal transducer and activator of transcription (STAT-1). Inhibition of these pathways with pyrrolidine dithiocarbamate, PD 98059, and fludarabine, respectively, attenuated GA-induced IL-8 secretion. Rosiglitazone dose-dependently attenuated GA-induced IL-8 and ICAM-1 signals in PTEC and completely abolished GA-induced STAT-1 signals but had no effect on NF-kappaB and MAPK activation. These findings suggest that AGE stimulate renal tubular expression of adhesion molecule and chemokine that together may account for the transmigration of inflammatory cells into the interstitial space during diabetic tubulopathy. Such proinflammatory phenotype may be partially modified by PPAR-gamma ligation through STAT-1 inhibition independent of NF-kappaB transcriptional activity and MAPK signaling.

Cell Line↗
PubMed2006

Ganoderma extract prevents albumin-induced oxidative damage and chemokines synthesis in cultured human proximal tubular epithelial cells.

BACKGROUND: Ganoderma lucidum (Ganoderma or lingzhi) is widely used as an alternative medicine remedy to promote health and longevity. Recent studies have indicated that components extracted from Ganoderma have a wide range of pharmacological actions including suppressing inflammation and scavenging free radicals. We recently reported that tubular secretion of interleukin-8 (IL-8) induced by albumin is important in the pathogenesis of tubulointerstitial injury in the proteinuric state. In this study, we explored the protective effect of Ganoderma extract (LZ) on albumin-induced kidney epithelial injury. METHODS: Growth arrested human proximal tubular epithelial cells (PTECs) were incubated with 0.625 to 10 mg/ml human serum albumin (HSA) for up to 72 h. HSA induced DNA damage and apoptosis in PTEC in a dose- and time-dependent manner. Co-incubation of PTEC with 4-64 microg/ml LZ significantly reduced the oxidative damage and cytotoxic effect of HSA in a dose-dependent manner (P<0.001). Increased release of IL-8 and soluble intercellular adhesion molecules-1 (sICAM-1) in PTEC induced by HSA was ameliorated by co-incubation with Ganoderma (16 microg/ml). To explore the components of LZ that exhibited most protective effect in HSA-induced PTEC damages, LZ was further separated into two sub-fractions, LZF1 (MW <30 kDa) and LZF2 (MW <3 kDa), by molecular sieving using millipore membrane. PTEC were incubated with 5 mg/ml HSA in the presence of different doses of LZF1, LZF2 or unfractionated LZ. RESULTS: There was no difference in the degree of protection from HSA-induced cytotoxicity or oxidative DNA damage between different fractions of LZ. However, low molecular weight LZ (<3 kDa) was most effective in reducing sICAM-1 released from HSA-activated PTEC whereas the high molecular weight LZ (unfractionated LZ) was more effective in diminishing IL-8 production. CONCLUSIONS: Our results suggest that Ganoderma significantly reduces oxidative damages and apoptosis in PTEC induced by HSA. The differential reduction of IL-8 or sICAM-1 released from HSA-activated PTEC by different components of the LZ implicates that components of Ganoderma with different molecular weights could play different roles and operate different mechanisms in preventing HSA-induced PTEC damage.

Albumins↗
PubMed2006

Viral nephropathy.

Viral infections can cause many glomerular diseases. The diagnostic criteria for virus-related nephropathy include detailed clinical and laboratory data, and tissue molecular analysis. Several mechanisms are involved in the pathogenesis of virus-related nephropathy, including tropism of the virus in the kidney, induction of abnormal immune complexes, direct cytopathogenic effects, and multiorgan failure. Hepatitis B virus is associated with membranous nephropathy and mesangiocapillary glomerulonephritis in endemic areas. Hepatitis C virus causes various forms of glomerulonephritis, including cryoglobulinemia-mediated glomerulonephritis. Infection with HIV is associated with a collapsing focal segmental glomerulosclerosis, a distinctive disease that affects mainly Africans and African Americans. In the course of HIV infection, other types of immune complex glomerulonephritis can occur, most frequently in whites. Recent reports indicate a role for parvovirus B19 in 'idiopathic' collapsing focal segmental glomerulosclerosis. Both hantaviruses, and coronaviruses associated with severe acute respiratory syndrome, can lead to acute renal failure. Renal biopsy followed by appropriate serological and molecular testing is essential for defining virus-related glomerular lesions and guiding prognostic and therapeutic evaluation.

Humans↗
PubMed2006

Effect of rapamycin on renal ischemia-reperfusion injury in mice.

The aim of this study was to determine the effect of rapamycin on renal ischemia-reperfusion injury (IRI) in mice. Renal IRI was induced in male BALB/c mice by clamping both renal pedicles for 45 min. The mice were treated with either vehicle or rapamycin (2 mg/kg/day) by oral gavage, starting 1 day before the IRI and continued daily till killing. The mice were killed on days 1, 3 and 7 after the operation. The severity of the renal IRI was assessed by serum creatinine levels and renal histology. Proliferation of renal tubular cells was quantified by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). One day after the IRI, the serum creatinine levels of rapamycin-treated mice were significantly higher than those of the vehicle-treated mice. Kidney sections from rapamycin-treated mice showed more marked tubular damage and significantly lower number of PCNA-positive cells. The number of PCNA-positive cells in the rapamycin-treated mice remained significantly lower on day 3 after the IRI. By day 7 after the IRI, the serum creatinine levels, renal histology and positive PCNA staining in the kidney sections became similar between the two treatment groups. We conclude that in this murine model of renal IRI, rapamycin treatment aggravates renal IRI during the first 3 days after the insult. This effect might be mediated, at least partly, through inhibition of renal tubular cell proliferation.

Animals↗
PubMed2005

Mannose binding lectin level and polymorphism in patients on long-term peritoneal dialysis.

BACKGROUND: Infection is a leading cause of mortality and morbidity in patients with end-stage renal disease. The increased susceptibility to infection is probably secondary to the impaired immune defence in uraemia and other co-morbid factors such as diabetes mellitus. Peritonitis remains the most common and major complication in the treatment modality of peritoneal dialysis (PD) for uraemic patients. Mannose binding lectin (MBL) is a calcium dependent C-type lectin that acts as an important first line defence mechanism against infection by its capability to activate the complement system and enhance phagocytosis. METHODS: We examined whether serum concentration of MBL and the point mutation of MBL may act as a risk factor in PD-related peritonitis. We studied four groups of dialysis patients: PD patients with two or more episodes of peritonitis, peritonitis-free PD patients, haemodialysis (HD) patients not previously on PD, and HD patients who were converted from PD due to technique failure following peritonitis-related abdominal adhesion. Results. Both homozygous and heterozygous patients had profoundly reduced serum level of MBL. The codon 54 point mutation rate amongst our dialysis patients was comparable with that of healthy subjects. Dialysis patients had a significantly lower serum level of MBL than healthy controls independent of the MBL gene mutation or the mode of dialysis treatment. Patients on PD with codon 54 point mutation were found to have a lower serum MBL level compared with HD patients with similar MBL gene mutation. However, we found no difference in the serum MBL level or frequency of codon 54 point mutation between four groups of dialysis patients. CONCLUSIONS: Dialysis patients have lower MBL levels that may increase the susceptibility of infection. However, the existence of other risk factors such as connection technique, nasal bacterial carriers, bowel pathology and personal hygiene precludes the MBL level as the sole primary factor for peritonitis in patients on maintenance PD treatment.

Adult↗
PubMed2005

Tubular expression of angiotensin II receptors and their regulation in IgA nephropathy.

Enhanced renal expression for the renin-angiotensin system (RAS) is detected in IgA nephropathy (IgAN). Previous data showed an altered glomerular expression of angiotensin II type 1 receptor (AT1R), suggesting a regulatory response to high intrarenal angiotensin II (Ang II) concentration in IgAN. In this study, the expression and regulation of Ang II receptors were examined in human proximal tubular epithelial cells (PTEC) in IgAN. Tubular expression of AT1R and Ang II type 2 receptor (AT2R) was increased in IgAN. In vitro culture experiment showed that the upregulation of Ang II receptors was not due to the direct effect of IgA but the indirect effect after IgA deposition on human mesangial cell. When PTEC were cultured with conditioned culture medium from human mesangial cells activated with IgA, Ang II production was upregulated, leading to inflammation and apoptosis via the AT1R and AT2R, respectively. Sequential expression of Ang II receptors determined the injury of PTEC induced by mediators in the conditioned medium. The initial interaction between Ang II and AT1R activated both protein kinase C and mitogen-activated protein kinase pathways, leading to inflammatory responses. This early AT1R-dependent event was followed by upregulation of AT2R expression and continued Ang II release. The interaction between Ang II and AT2R subsequently led to expression of cleaved poly[ADP-ribose] polymerase through downregulation of the mitogen-activated protein kinase pathway. The data suggest that appropriate control of Ang II receptor activities in PTEC may ameliorate tubulointerstitial injury in IgAN.

Angiotensin II↗
PubMed2005

Glucose degradation products downregulate ZO-1 expression in human peritoneal mesothelial cells: the role of VEGF.

BACKGROUND: Glucose degradation products (GDPs) are formed during heat sterilization of peritoneal dialysis fluid and, to a lesser extent, during their prolonged storage. In vitro studies have demonstrated that GDPs impair functions of peritoneal mesothelial cells, including proliferation, viability and cytokine release. In the present study, we studied the acute effect of GDPs on the expression of tight junction-associated protein, zonula occludens protein 1 (ZO-1), in human peritoneal mesothelial cells (HPMC). The role of the vascular endothelial growth factor (VEGF) induced by GDPs in the expression of ZO-1 was also examined. METHODS: HPMC were cultured with GDPs, including 2-furaldehyde (FurA), methylglyoxal (M-Glx) and 3,4-dideoxyglucosone-3-ene (3,4-DGE). The expression of ZO-1 and the synthesis of VEGF were examined. To define the role of VEGF on the regulation of ZO-1 expression, HPMC were cultured with GDPs in the presence or absence of neutralizing antibody to VEGF. The signal pathways involved in VEGF synthesis induced by GDPs were also characterized. RESULTS: ZO-1 expression in HPMC was downregulated in a time- and dose-dependent manner following culture with subtoxic concentrations of GDPs (FurA, M-Glx and 3,4-DGE). All three GDPs increased VEGF synthesis in HPMC. Exogenous VEGF downregulated the expression of ZO-1 and neutralizing anti-VEGF antibody reversed the effect of GDPs on ZO-1 expression in HPMC, suggesting the action of GDPs on ZO-1 expression was mediated by VEGF. All three GDPs activated the p42/p44 mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) signal transduction pathways. The GDP-induced VEGF and transforming growth factor (TGF)-beta synthesis in HPMC was partially reduced by either the p42/p44 MAPK inhibitor (PD98059) or the PKC inhibitor (staurosporine). More importantly, the VEGF and TGF-beta synthesis induced by GDPs in HPMC was completely blocked by synergistic action of both inhibitors. CONCLUSIONS: We have demonstrated that short-term exposure to GDPs downregulates ZO-1 expression in HPMC through the generation of VEGF. Our study provides evidence that GDPs can directly induce VEGF and TGF-beta production in HPMC through the activation of p42/44 MAPK and PKC signal transduction pathways.

Aldehydes↗
PubMed2005

Differential expression of aquaporins in the kidneys of streptozotocin-induced diabetic mice.

BACKGROUND AND AIM: Aquaporins (AQPs) are members of the water channel family and are important in renal physiology as it affects urinary concentration. The downregulation of aquaporins is often observed in polyuria associated with acquired nephrogenic diabetes insipidus. In this study, we examined the expression of AQP1, AQP2, AQP3 and AQP4 in streptozotocin (STZ)-induced diabetic mice. RESULTS: By semiquantitative reverse transcription-polymerase chain reaction, we detected no change in the gene expression of AQP1 or AQP4 in whole kidney among STZ-induced diabetic mice (STZ mice) and sham (control group that received citrate buffer injection only). In contrast, we found less AQP2 or AQP3 mRNA expression in the whole kidney from STZ mice. Immunoblotting studies confirmed no difference in AQP1 or AQP4 protein expression of whole kidney between STZ mice and sham. However, there was less AQP2 or AQP3 protein expression in the whole kidney from STZ mice as compared to sham. By immunochemical staining, the reduction of AQP2 protein was localized to the principle cells of the collecting ducts. The expression of cortical AQP3 (especially the outer cortex, the S1 and S2 segments of the proximal tubules) was downregulated in STZ mice whereas the expression of AQP3 protein in medullary collecting ducts was similar to that of sham. CONCLUSION: Our results reveal that the water transport in urinary concentration involves the downregulation of AQP2 and AQP3 expression in STZ mice.

Animals↗
PubMed2005

Seroprevalence of Helicobacter pylori in Chinese patients on continuous ambulatory peritoneal dialysis.

BACKGROUNDS AND AIMS: There is relatively little data on the seroprevalence of Helicobacter pylori in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). This study aims at establishing the seroprevalence of and the factors associated with H. pylori infection in Chinese CAPD patients. METHODS: All CAPD patients from a single dialysis centre were invited to participate in the study. Diagnosis of H. pylori infection was made serologically by the pylori DTect ELISA method. Dyspeptic symptoms were assessed by the Hong Kong Index of Dyspepsia (HKID) Questionnaire. Demographic, clinical and laboratory parameters were correlated with the H. pylori serology results. RESULTS: One hundred and thirty-six Chinese CAPD patients were included in the study. The mean age of the patients was 61.8 +/- 12.5 years with a male to female ratio of 1:1.4. The mean duration of CAPD was 54 +/- 42 months. Thirty-five patients (26%) have positive serology against H. pylori. Nineteen patients had a HKID score of >16. There was no association between H. pylori seropositivity and dyspeptic symptoms (P = 0.62). Patients who were seropositive for H. pylori were significantly older (64.9 +/- 9.5 years vs 60.7 +/- 13.2 years, P < 0.05) and had lower KT/V-values than patients who were seronegative for H. pylori (1.88 +/- 0.3 vs 2.03 +/- 0.3, P < 0.05). Patients with positive or negative H. pylori serological status did not differ in terms of demographic parameters (e.g. sex, duration of CAPD), clinical factors (e.g. bodyweight, body mass index, hepatitis status, use of H(2) antagonists or proton pump inhibitors) and laboratory data (e.g. haemoglobin, serum urea, creatinine, albumin and parathyroid hormone levels). CONCLUSIONS: The seroprevalence of H. pylori infection among Chinese CAPD patients is 26%. Helicobacter pylori seropositivity is not associated with dyspepsia. Older age and lower KT/V-values appear to be associated with the development of H. pylori seropositivity in our dialysis population.

Aged↗
PubMed2005

Treatment for lupus nephritis: a revisit.

The optimal treatment of severe lupus nephritis remains unclear. Regimens consisting of steroid and cyclophosphamide (CYC) appear to be most effective. Infection and gonadal toxicity is a major concern of CYC use in patients of reproductive age. In addition, failure to respond or refractory to CYC treatment may lead to the development of end-stage renal disease. Mycophenolate mofetil (MMF) is a new immunosuppressive agent that selectively inhibits activated lymphocytes and renal mesangial cells. Data from experimental lupus nephritis and controlled studies, albeit small and lacking statistical power, have revealed that MMF is as effective in lupus patients as CYC in the induction of renal remission or as maintenance therapy to reduce renal flare in the short term. The significantly less ovarian toxicity and infection when compared to CYC are particularly attractive for the consideration of MMF in lupus nephritis. The potential of other new therapeutic agents is discussed together with the need for patient recruitment in future trials of lupus nephritis to address the importance of ethnicity as well as histological grading.

Humans↗
PubMed2005

Pathogenesis of lupus nephritis: an update.

Lupus nephritis (LN) is a prototypic autoimmune disease. Its immunopathogenesis is characterized by the loss of self-tolerance. In this article, we review our current understanding of the disease mediators of LN. There is ample evidence to suggest a pathogenic role of nephritogenic autoantibodies. These antibodies cross react with nucleosomal epitopes, and the in vivo generation of nucleosomes requires apoptosis. Furthermore, there is an intriguing and paradoxical relationship between complement and systemic lupus erythematosus (SLE). Immune complex-mediated activation of complement through the classic pathway is traditionally believed to be a major mechanism by which tissue injury occurs. In contrast, hereditary deficiencies of complement components increase the risk of SLE. Finally, the roles of reactive nitrogen and oxygen species are emphasized.

Animals↗
PubMed2005

Chronic viral hepatitis in hemodialysis patients.

Ever since the first outbreaks of hepatitis in hemodialysis units in the late 1960s, a number of hepatotropic viruses transmitted by blood and other body fluids have been identified. This review summarizes the current state of knowledge regarding these blood-borne agents from an epidemiologic and preventive perspective. Data source and study selection were obtained from research and review articles related to the epidemiology of viral hepatitis in hemodialysis and indexed on Medline and Embase from 1965 to 2004. Hepatitis B virus (HBV) was the first significant hepatotropic virus to be identified in hemodialysis centers. HBV infection has been effectively controlled by active vaccination, screening of blood donors, the use of erythropoietin, and segregation of HBV carriers. To date, HBV remains an important cause of morbidity in endemic areas. Hepatitis delta virus is a defective virus that can only infect HBV-positive individuals. Hepatitis C virus is the most significant cause of non-A, non-B hepatitis and is mainly transmitted by blood transfusion. The introduction in 1990 of routine screening of blood donors for HCV contributed significantly to the control of HCV transmission. An effective HCV vaccine remains an unsolved challenge, however. Pegylation of interferon-alpha has made it possible to treat HCV-positive dialysis patients. Unexplained sporadic outbreaks of hepatitis by the mid-1990s prompted the discovery of hepatitis G virus and hepatitis GB virus C in 1995 and the TT virus in 1997. Although epidemiologic analyses revealed high prevalence rates of both viruses in the hemodialysis population, their exact role in liver disease has yet to be determined. The vigilant observation of guidelines on universal precaution and regular virologic testing are the cornerstones of the effective control of chronic hepatitis in the setting of hemodialysis.

Antiviral Agents↗
PubMed2005

Mycophenolate mofetil alleviates persistent proteinuria in IgA nephropathy.

BACKGROUND: Mycophenolate mofetil (MMF) is increasingly used to treat primary glomerulopathies. Its effectiveness in IgA nephropathy (IgAN) remains unclear. METHODS: Forty IgAN patients with persistent proteinuria (>1 g/24 hours) despite conventional treatment with blockers of the renin-angiotensin system were randomized to receive MMF for 24 weeks (group 1) or continue conventional therapy (group 2), and followed for 72 weeks. The primary end point was reduction of proteinuria by 50% or more over entry level. RESULTS: Sixteen patients (80%) in group 1 versus six patients (30%) in group 2 reached the primary end point (P= 0.0019). Time-averaged change in proteinuria showed a significant decline in group 1, while control subjects displayed a modest rise (P= 0.003). By 72 weeks, the mean proteinuria was 62.0 +/- 7.7% (P= 0.003) and 120.5 +/- 14.1% (P= 0.351) that of the corresponding baseline value in group 1 and group 2, respectively. There was concomitant increase in serum albumin and decrease in serum IgA levels in group 1 but not group 2 patients. Baseline histologic grades, blood pressure control, and the rates of change in serum creatinine and creatinine clearance were not different between the two groups. Normalization in binding of polymeric IgA to cultured mesangial cells and serum interleukin-6 (IL-6) levels, which sustained to study end, was observed in group 1 but not group 2 subjects. CONCLUSION: In selected patients with IgAN, MMF is effective in lowering proteinuria and ameliorating some of the putative pathogenetic abnormalities.

Adult↗
PubMed2005

Lamivudine in hepatitis B-associated membranous nephropathy.

BACKGROUND: Although lamivudine is effective for treatment of chronic hepatitis B (HBV) infection, its potential therapeutic impact on HBV-related membranous nephropathy (MN) in adults has not been characterized. METHODS: We treated 10 HBsAg-positive patients with biopsy-proven MN, elevated serum alanine aminotransferase (ALT), and HBV-DNAemia (group 1), and compared their clinical course with 12 patients diagnosed to have HBV infection, elevated serum ALT, and MN in the pre-lamivudine era (group 2). RESULTS: Baseline demographic and clinical parameters were not different between the 2 groups. In group 1, lamivudine treatment was associated with significant reduction in proteinuria, increase in serum albumin, normalization of ALT levels, and disappearance of circulating HBV-DNA during the first year. Four (40%) and 6 (60%) patients went into complete remission (proteinuria <0.3 g/d) at 6 and 12 months, respectively. In group 2, significant proteinuria persisted during the first year. One (8.3%) and 3 (25%) patients went into remission. Cumulative 3-year renal survival [using end-stage renal disease (ESRD) as primary end point] was 100% in group 1 and 58% in group 2 (P= 0.024, log rank test). Blood pressure control reached the target of below 130/85 mm Hg in both groups. Lamivudine was well tolerated and not associated with any adverse events. Hepatic decompensation or malignancy was not observed during follow-up in both groups. CONCLUSION: HBV-related MN leads to ESRD in a significant proportion of patients before the advent of antiviral therapy. Lamivudine treatment improves renal outcome in HBV carriers with MN and evidence of liver disease.

Adult↗