I. K. P. Cheng

Hepatitis C in renal transplant recipients

Sera from 130 renal transplant recipients were tested for antibody to hepatitis C virus (anti-HCV). Anti-HCV was detected in 6.2% of patients: 15.4% of patients who had maintenance hemodialysis (HD) and 2.2% of those who had continuous ambulatory peritoneal dialysis (CAPD) before transplantation (P<0.05). The similarity in prevalence of anti-HCV with patients currently on dialysis and the absence of transfusion during posttransplant follow-up suggest that most patients acquired HC V infection through transfusion during dialysis. The proportion of anti-HCV-positive patients who had one or more episodes of elevation in serum transaminase level was similar to that of hepatitis B surface antigen (HBsAg)-positive patients, 75% vs. 72.2%. However, anti-HCV was only detected in 25% of HBsAg-negative patients who had recurrent elevations in serum transaminase level. It is not clear whether the low prevalence of anti-HCV in these patients is related to the presence of other non-A, non-B hepatitis virus (es) or a decrease in titer of anti-HCV secondary to immunosuppression posttransplantation.

The impact of donor and recipient hepatitis B surface antigen status on liver disease and survival in renal transplant recipients.

Ninety-eight renal transplant recipients who had been followed for 1–6.5 years (median 3.2 years) were reviewed to determine the effect of donor and recipient hepatitis B surface antigen status on the incidence of hepatitis and on patient survival. The cumulative risk of developing hepatitis posttrans-plant was significantly higher in hepatitis B surface antigen-positive versus hepatitis B surface antigen-negative patients (P=0.001). Nine (60%) of 15 patients who were hepatitis B surface antigen-positive prior to transplantation, 3 (75%) of 4 patients who became hepatitis B surface antigen-positive after transplantation, and 17 (22%) of 79 patients who were persistently hepatitis B surface antigen-negative developed hepatitis posttransplant. Five hepatitis B surface antigen-negative patients received allografts from hepatitis B surface antigen-positive donors. None of the five, including one who was initially seronegative, became hepatitis B surface antigen-positive posttransplant. Of the four patients who became HBsAg-positive posttransplant, three received kidneys from donors of unknown HBsAg status in China, while one was transplanted with a kidney from a HBsAg-negative donor. In summary, we found that the risk of developing hepatitis after renal transplantation was significantly higher in hepatitis B surface antigen-positive patients. However, both patient and graft survival were similar in hepatitis B surface antigen-positive and hepatitis B surface antigen-negative patients. The transplantation of kidneys from HBsAg-positive donors to HBsAg-negative patients did not result in clinically significant hepatitis or chronic HBsAg carriage. De novo hepatitis B infection may arise from sources other than the kidney itself.

Isoniazid induced encephalopathy in dialysis patients

Three dialysis patients with extrapulmonary tuberculosis developed confusion 4-14 days after commencement of treatment with anti-tuberculosis drugs, despite the use of prophylactic pyridoxine. Full recovery of conscious state resulted within 1 week in all patients after stopping isoniazid. In 2 patients confusion recurred on rechallenge of the drug. The risk factors of isoniazid induced encephalopathy and the dosage of isoniazid in uraemic patients were discussed.

Focal Sclerosing Glomerulopathy Risk Factors of Progression and Optimal Mode of Treatment

Focal sclerosing glomerulopathy and especially focal segmental glomerulosclerosis (FSGS) have been recognized as a distinct clinical entity, however, there still exist controversies in terms of prognostic risk factors of progression and optimal mode of treatment. A total of 32 patients (2 with focal global sclerosis; FGS, the remainder with FSGS) were followed up for a mean period of 82 months (3–240 months). Fourteen presented with nephrotic syndrome and 18 had proteinuria with or without hypertension. Thirteen patients, all of whom except 1 were nephrotic, received steroid treatment with or without other immunosuppressive agents (cyclophosphamide/cyclosporin A/azathioprine). Three of the steroid-treated remained stable in complete remission; 5 nephrotic non-responders had renal death. The mean slope of 1/creatinine versus time for steroid-treated and non-treated groups was −0.23 and −0.043, respectively (p=0.04), suggesting that nephrotic range proteinuria might be prognostically important. However, for the population of FSGS/FGS as a whole, only the initial serum creatinine predicted renal survival (p=0.001 by Coxs regression model). Hypertension and hypercholesterolaemia were not important variables by themselves. Nevertheless, we found that the 9 patients treated with antihyperlipidaemics (gemfibrozil/probucol/cholestyramine/maxEPA) fared better, mean slope being −0.023 versus −0.103 for non-treated, though not reaching statistical significance (p=0.96). Controlled prospective study involving a larger number of patients might be worthwhile.

A randomized prospective comparison of nadolol, captopril with or without ticlopidine on disease progression in IgA nephropathy

To determine if angiotensin converting enzyme inhibitors (ACEI) and antiplatelet agents have any added advantages over beta‐blockers in preventing disease progression in IgA nephropathy (IgAN), 52 patients with IgAN with at least two features suggestive of progressive disease, namely, proteinuria >1 gm/day, mean blood pressure (MBP)>107 mmHg, serum creatinine 0.12–0.4 mmol/L and the presence of glomerulosclerosis and/or tubulointerstitial fibrosis on initial biopsy were randomized to receive nadolol (N), captopril (C) and captopril plus ticoplidine (CT). In hypertensive subjects, the dose N and C was adjusted to normalize MBP. In normotensive subjects the dose was adjusted to achieve a reduction of MBP of 5–10mmHg. Five patients withdrew prematurely before reaching the end of the study period. The results after a minimal period of 3 years follow‐up were available in the remaining 47 patients (n=16, 12 and 19 in groups N, C and CT, respectively). Target of blood pressure (BP) treatment was achieved in all patients and the post‐treatment MBP was comparable among the three groups. In C and CT, peripheral blood renin increased significantly while in CT, in vitro platelet aggregation decreased significantly following treatment. Urinary protein and albumin excretion decreased significantly in all treatment groups but there was no difference among the three groups. Progression of renal failure as measured by life table analysis of the percentage of patients with doubling of serum creatinine and by the slope of the reciprocal of serum creatinine (mean±SEM: −0.021±0.014; −0.016±0.010 and −0.017±0.008 for N, C and CT, respectively) and of glomerular filtration rate as measured by plasma disappearance of injected Cr51EDTA over time (mean±SEM: −0.556±0.157, −0.739±0.304 and −0.543±0.274 for N, C and CT) were similar among the three groups. In this small comparative study, ACEI does not appear to be better than long‐acting beta‐blocker in retarding disease progression in patients with IgAN and ticlopidine confers no additional benefit.

Crescentic IgA glomerulonephritis following interleukin-2 therapy for hepatocellular carcinoma of the liver

A patient who developed crescentic IgA nephropathy following treatment with recombinant interleukin-2 (rIL2) and lymphokine-activated killer (LAK) cell therapy for hepatocellular carcinoma was reported. Cessation of rIL2 and LAK cell treatment plus plasmapheresis and steroid therapy was successful in achieving partial improvement and stabilization of renal function. This is the first case report of biopsy-documented glomerulonephritis developing after IL2 and LAK cell therapy. This provides indirect in vivo evidence for the role of IL2 in mediating glomerular injury in IgA nephropathy.

A randomized prospective comparison of oral versus intraperitoneal ofloxacin as the primary treatment of CAPD peritonitis

Summary: Oral ofloxacin has been successfully used in our centres for the primary treatment of peritonitis complicating continous ambulatory peritoneal dialysis (CAPD). In view of the progressive rise in the resistance rate to ofloxacin among peritoneal bacterial isolates, a study was conducted to determine if oral ofloxacin remains a viable first line treatment for CAPD peritonitis in our centres and if the result can be improved by changing from an oral to an intraperitoneal (i.p.) route. In patients on three 2 L daily CAPD exchanges, ofloxacin given at the i.p. dosage of 200 mg loading followed by 25 mg/L of peritoneal dialysate achieved overnight trough peritoneal levels which are at least four times the minimal 90% inhibitory concentration (MIC90) of most bacterial pathogens without significant accumulation in the systemic circulation. This i.p. dosage was therefore chosen for the clinical study and the result was compared to that using ofloxacin given in the oral dosage of 400 mg loading followed by 300 mg once daily as maintenance. of all the recruited episodes, 35 were eligible for analysis. the overall primary cure rate including primary failures and relapses was 55.6% (10/18) in the oral treatment group and 70.6% (12/17) in the i.p. treatment group. the corresponding figures for gram positive bacterial (g +) infections were 36.4% and 50%, for gram negative bacterial (g ‐) infections were 66.7 and 80% and for culture negative infections were 75 and 80%. In culture positive cases, all treatment failures were due to resistant infections which were observed in 42.3% of all bacterial isolates, 47.1% of g + isolates and 33.3% of g ‐ isolates. Due to the high background level of bacterial resistance among our CAPD population, ofloxacin monotherapy given either by the oral or the i.p. route can no longer be recommended for the primary treatment of CAPD peritonitis.

Non-immune therapy of IgA glomerulonephritis

Summary: The involvement of the IgA immune system and complement components in IgA glomerulonephritis (IgAGN) has prompted the use of immunosuppressive drugs in therapy, but none has so far been shown to alter the natural course of the disease. Because most patients with IgAGN present during the chronic phase of their illness, at the time when the initiating immune events may no longer be active, nonimmune therapy which targets the common pathway of progressive renal injury is likely to be more useful. There is increasing evidence that angiotensin‐converting enzyme inhibitors (ACEI) reduce proteinuria and renal injury in patients with IgAGN, and this effect may be observed in both normotensive and hypertensive patients. Yet to be determined is whether this effect is specific for ACEI and whatever other effective antihypertensive drugs may achieve a similar result. Fish oil has recently been shown to retard the progression of renal failure in patients with aggressive IgAGN, but a narrow therapeutic window appears to exist for this form of treatment. Antiplatelet agents on their own appear to be ineffective but in combination with anticoagulation (low dose warfarin) have been shown to have an antiproteinuric effect and may preserve renal function in patients with progressive disease. Future directions of non‐immune therapy of IgAGN include evaluation of the renoprotective effect of angiotensin II receptor antagonists, free‐radical scavengers and antilipid drugs. More work should also be done to identify factors which put the patients at risk of developing progressive disease and which predict therapeutic response, as has been done recently with the identification of the deletion polymorphism of the angiotensin‐converting enzyme gene as a marker of progressive disease and therapeutic response to ACEI in patients with IgAGN.

Haematological Changes after Renal Transplantation: Differences between Cyclosporin-A and Azathioprine Therapy

Haematological changes after renal transplantation in 76 patients were reviewed and the differences observed between patients treated with cyclosporin-A and prednisolone and those treated with azathioprine and prednisolone were compared. Erythrocytosis defined as haemoglobin concentration equal to or exceeding 17 g/dl occurred in 25% of patients treated with cyclosporin-A and in 11.4% of patients treated with azathioprine. Only one patient, who received cyclosporin-A, had clinical evidence of thrombosis. Eight patients treated with cyclosporin-A and five treated with azathioprine had therapeutic venesections. There was no difference in the incidence of putative risk factors for post-transplant erythrocytosis between the two groups.

Delayed recurrent thromboembolism of the allograft kidney

Renal artery thromboembolism is a rare event in native kidneys and has never been reported to occur in allograft kidney. We report a case of allograft kidney infarction secondary to embolisation from thrombus in the hypogastric artery supplying the allograft on two separate occasions 1 and 2 years after transplant. Anticoagulation therapy alone was given and the patient responded well with partial recovery of renal function.