Stephen K. N. Ho

A 3-year, prospective, randomized, controlled study on amino acid dialysate in patients on CAPD

BACKGROUND Malnutrition is prevalent in patients on continuous ambulatory peritoneal dialysis (CAPD) and confers a poor prognosis. Inadequate nutrient intake is an important contributing factor. Although short-term studies have shown mild to modest nutritional benefit with amino acid dialysate, its long-term effects and tolerability remain obscure. METHODS The authors have performed a 3-year, randomized, prospective, controlled study of amino acid dialysate in malnourished Chinese patients on CAPD. Sixty patients were assigned randomly to either replace 1 exchange daily with amino acid dialysate (Nutrineal; DAA group, n = 30) or to continue with dextrose dialysate (Dianeal; DD group, n = 30). RESULTS The 2 groups had similar mortality, hospitalization duration, serial C-reactive protein levels, and drop-out rates during the study. Biochemical nutritional parameters including albumin and cholesterol decreased in the DD group but remained stable or increased in the DAA group. The composite nutritional index did not differ between the 2 groups throughout the study period. Triglyceride decreased only in DAA-treated patients. Normalized protein equivalent of nitrogen appearance and dietary protein intake showed a sustained increase only in DAA patients. The nutritional benefit of DAA appeared more prominent in women, whose lean body mass and body mass index was maintained with DAA but not with DD. Mass transfer area coefficient for creatinine increased in DAA-treated patients, whereas that for urea as well as macromolecular restriction coefficients remained stable. Total Kt/V(urea) and daily ultrafiltration volume were similarly maintained in the 2 groups throughout the study. CONCLUSION Long-term administration of amino acid dialysate is well tolerated and presents a means to improve the nutritional status in high-risk patients. The current study, however, has not shown a significant effect of amino acid dialysate on patient survival.

Pilot study of pegylated interferon‐alpha 2a in dialysis patients with chronic hepatitis C virus infection

Aim:  Pegylated interferon (PEG‐IFN) combined with ribavirin is recommended for the treatment of chronic hepatitis C virus (HCV) infection in patients without renal failure. The optimal treatment of hepatitis C in dialysis patients remains to be established. A high incidence of adverse effects has been observed with conventional interferon and PEG‐IFN alpha‐2b in dialysis patients.

Crescentic nodular glomerulosclerosis secondary to truncated immunoglobulin α heavy chain deposition

Nodular glomerulosclerosis secondary to deposition of monoclonal immunoglobulin (Ig) light chains with or without heavy chains is a recognized clinicopathological entity. Recent reports have demonstrated that an identical glomerular lesion may also occur as a result of truncated tau Ig heavy chain deposition. We investigated the nature of Ig deposits in a patient who presented with rapidly progressive renal failure secondary to crescentic nodular glomerulosclerosis. This patient had a relapsing clinical course responsive to treatment with steroid and cyclophosphamide therapy. In this case, both the glomeruli and tubular basement membrane contained granular immune deposits that were reactive to polyclonal antibodies against alpha but not tau or mu Ig heavy chains and nonreactive to anti-kappa and anti-lambda light chain reagents. A monoclonal population of plasma cells secreting alpha and kappa chains was present in the patients marrow despite the finding of a normal percentage of plasma cells. Serum Immunoelectrophoresis was normal, but immunofixation demonstrated the presence of a monoclonal alpha/kappa band. Immunoblot under dissociating and nondissociating conditions showed that both the patients urine and serum contained Ig fragments that comprised dimer or monomer of an abnormally short alpha Ig heavy chain (approximately 26 kd) with or without associated kappa light chain. The identity of the abnormal serum alpha Ig heavy chain with that of the glomerular Ig deposits was supported by the finding that both were nonreactive against alpha 1 and alpha 2 subclass-specific monoclonal antibodies despite their reactivity to polyclonal antibodies. Because these monoclonal antibodies would react with structural determinants, which differ between alpha 1 and alpha 2 Ig heavy chains but not those common between them, and because the differences in amino acid sequence between the two largely lie in the CH1 and CH2 domains of the alpha Ig heavy chain, it is hypothesized that the abnormally short alpha Ig heavy chain produced by plasma cells in this patient contains deleted CH1 and CH2 domains similar to the findings in patients with tau Ig heavy chain deposition disease.

Prospective Study on Lamivudine‐Resistant Hepatitis B in Renal Allograft Recipients

The natural history of lamivudine‐resistant hepatitis B virus (HBV) infection in renal transplant recipients (RTx) is unclear, despite its increasing incidence. Twenty‐nine HBsAg‐positive RTx with rising HBV DNA received lamivudine therapy. The course of lamivudine‐resistant HBV infection was studied prospectively. During 68.7 ± 12.5 months of follow‐up, 14 (48.3%) patients developed lamivudine resistance, at 10–35 months (mean 16.9 ± 7.0). All showed mutant sequences at codons 552 and 528 of the YMDD motif, while 13 patients demonstrated wild‐type sequence at codon 555. Lamivudine resistance was unrelated to patient demographics, HBeAg status/sero‐conversion, or genotype. Following resistance, HBV DNA and alanine aminotransferase showed an initial increase followed by spontaneous gradual reduction. The subsequent peak HBV DNA was lower (1.26 ± 1.09 × 109 vs. 6.26 ± 12.23 × 109 copies/mL, p = 0.011), while that of alanine aminotransferase was higher (196 ± 117 vs. 77 ± 47 iμ/l, p = 0.005), compared with pretreatment levels. Post‐resistance hepatitic flare occurred in 11 (78.6%) patients. This was transient in four (36.4%), but became chronic in six (54.5%) patients. Decompensation was noted in one patient during this flare, but all survived. We conclude that drug resistance is prevalent in lamivudine‐treated RTx. Despite a lower ensuing peak viremia compared with baseline, hepatitic flare is common. While most patients have spontaneous resolution, a minority may develop potentially fatal decompensation during the preceding exacerbation.

Efficacy of famciclovir in the treatment of lamivudine resistance related to an atypical hepatitis B virus mutant.

Reactivation of chronic hepatitis B virus (HBV) infection is a major cause of morbidity and mortality after renal transplantation. Although lamivudine is an effective treatment for chronic hepatitis B, the development of drug resistance due to mutations in the tyrosine-methionine-aspartate-aspartate (YMDD) motif is a major concern, especially in immunosuppressed patients who require prolonged therapy. Treatment with famciclovir has not been effective in the majority of patients who developed lamivudine resistance due to methionine-to-valine mutation at position 550, because this mutation has been uniformly associated with leucine-to-methionine mutation at position 526, a mutation that is associated with resistance to famciclovir. We describe a renal transplant recipient with an uncommon lamivudine-resistant HBV variant, in which methionine-to-valine/isoleucine mutation at position 550 was associated with wild-type sequence at position 526. The severe hepatitic flare consequent to the lamivudine resistance in this patient was successfully treated with famciclovir, indicating that both M550V and M550I mutants with preserved wild-type sequence at position 526 of HBV reverse transcriptase are susceptible to famciclovir. Our experience shows that famciclovir can be useful in selected patients with otherwise potentially fatal hepatitic flares related to lamivudine resistance, and that analysis of mutations in the HBV variant can be helpful in the choice of antiviral therapy.

Cystatin C assay for the detection of renal dysfunction in Chinese renal transplant recipients.

BACKGROUND Accurate and rapid assessment of kidney function in patients after renal transplantation is of major significance. We investigated whether cystatin C can accurately reflect creatinine clearance over the entire range of kidney graft function. The performance of serum cystatin C as a screening marker of reduced creatinine clearance in renal transplantation was evaluated and compared to serum creatinine. METHODS Serum cystatin C, serum creatinine and creatinine clearance were measured in 103 adult renal transplant recipients. The cystatin C assay was performed using particle-enhanced immunonephelometry. RESULTS We demonstrated a significant linear correlation between 1/cystatin C and creatinine clearance over the entire range of transplant function, comparable to that of creatinine. Cystatin C detected reduced creatinine clearance with higher sensitivity of 92.9% (95% CI 80.5-98.4%) than serum creatinine, 71.4% (95% CI 55.4-84.3%). From the receiver operating characteristic (ROC) plots, serum cystatin C is superior to serum creatinine at 90% and 95% sensitivity. CONCLUSIONS Serum cystatin C accurately reflects creatinine clearance over the entire range of transplant kidney function and is more efficacious than serum creatinine to detect reduced creatinine clearance in renal transplant recipients.

Increased survival of mesothelial cells from the peritoneum in peritoneal dialysis fluid.

Peritonitis remains the most important factor in patient morbidity and technical failure associated with continuous ambulatory peritoneal dialysis (CAPD). In vitro examination of bacterial infection of cultured human peritoneal mesothelial cells (HPMC) is an attractive approach to the study of peritonitis in CAPD, yet there are few reports on this subject. Previous studies have shown two limitations: (i) cell cultures of HPMC lasted for days only when incubated in culture medium and (ii) short‐term studies of <30min were done in HPMC when incubated with peritoneal dialysis fluid (PDF). Human peritoneal mesothelial cells, maintained in a conventional single chamber culture system with PDF alone, were unable to survive more than 40min. The present study was designed to prolong the viability of HPMC cultured in PDF, with the object of using cells under different conditions, such as that of simulating CAPD. HPMC were cultured using plastic microtiter plates, where they were grown to confluence and growth was arrested. PDF containing different concentrations of NaHCO3and human serum albumin was added. Cell viability after exposure for up to 24h was measured by trypan blue, Cell Death Detection ELISA and Annex‐V flow cytometry. The data confirmed the ‘toxic’ effect of PDF, with cell viability being <40% after 2h incubation in 4.25% glucose in PDF. However, the survival time of HPMC increased significantly in 4.25% glucose PDF at a physiological pH and even further after the addition of human albumin. These experimental conditions simulating CAPD may allow future in vitro studies of mesothelial physiology and peritonitis related to CAPD treatment.

Prevalence and significance of hepatitis GB virus-c/hepatitis G virus viremia in a large cohort of patients with chronic hepatitis B infection, with chronic hepatitis C infection, and on renal replacement therapy in Hong Kong.

A total of 455 patients were recruited to study the prevalence of hepatitis GB virus-C/hepatitis G virus viremia in Hong Kong. There was no significant increase in the prevalence of hepatitis GB virus-C viremia in asymptomatic hepatitis B virus- and hepatitis C virus-infected patients compared to that of controls (1.56% and 7.14%, respectively, vs 3.85%, both P = NS). Renal patients as a whole had a significantly higher prevalence of hepatitis GB virus-C viremia compared to that of controls (13.95% vs 3.85%, P = 0.0271). The duration of the replacement therapy, especially for patients with peritoneal dialysis was associated with a higher chance of hepatitis GB virus-C viremia. Among renal patients, renal transplanted patients had the highest prevalence of hepatitis GB virus-C viraemia (19.1%) probably because of a higher susceptibility as a result of immunosuppression. However, hepatitis GB virus-C viraemia did not cause liver biochemistry derangement in renal transplanted patients.