Beneficial effects of high-dose losartan in IgA nephritis.

AIM: Several short-term studies have reported the efficacy of high-dose ARB in reducing proteinuria in patients with diabetic nephropathy. The benefits of long-term high-dose ARB losartan in IgA nephritis have not been explored. METHOD: This was a 6-year randomized trial in 207 patients with IgA nephritis comparing high-dose ARB (losartan 200 mg/day) with normal dose ARB (losartan 100 mg/day), normal dose ACEI (20 mg/day) and low-dose ACEI (10 mg/day). Multivariate ANOVA was used to test the effect of drug treatment on both eGFR and total urinary protein (TUP). RESULTS: Comparing patients on high-dose ARB (n = 63) with those on normal dose ARB (n = 43), normal dose ACEI (n = 61) and low-dose ACEI (n = 40), patients on high Dose ARB had significantly higher eGFR (p < 0.0005) and lower proteinuria (p < 0.005) at the end of the study. The loss in eGFR was 0.7 ml/min/year for high-dose ARB compared to 3.2 - 3.5 ml/ min/year for the other 3 groups (p = 0.0005). There were more patients on high-dose ARB with improvement in eGFR compared to other 3 groups (p < 0.001). CONCLUSION: Data from this study suggest that high-dose ARB therapy is more efficacious in reducing proteinuria and preserving renal function when compared with normal dose ARB and ACEI. In Year 5, patients on high-dose ARB had a gain in eGFR suggesting that there is possibility of recovery of renal function in these patients on long-term high-dose therapy.

Obstetric outcomes in women with end-stage renal failure requiring renal dialysis.

OBJECTIVE: To study obstetric outcomes in women with end-stage renal failure undergoing chronic renal dialysis. METHODS: A retrospective review of the database from the High-Risk Pregnancy Clinic at Singapore General Hospital, Singapore. RESULTS: From 1995 to 2004, 7 women treated with chronic renal dialysis had a total of 11 pregnancies. There were 2 pregnancy losses at previable gestation ages and 9 live births. Median gestational age at delivery was 31 weeks, and mean birth weight was 1390 g. Seven newborns had a low birth weight and 5 required neonatal intensive care. Severe hypertension occurred in 4 women for a total of 7 pregnancies. Other complications included polyhydramnios (n=2), preterm prelabor rupture of membranes (n=2), obstetric cholestasis (n=2), postpartum hemorrhage (n=1), thrombosis of the arteriovenous fistula (n=2), postpartum peritonitis (n=1), and fetal anomaly (n=1). There were no maternal deaths. CONCLUSION: Such pregnancies are high-risk, particularly because of maternal hypertension and prematurity. They should be managed by multidisciplinary teams, and prepregnancy counseling should not be neglected.

ACE gene polymorphism and disease progression of IgA nephropathy in Asians in Singapore.

The deletion polymorphism of the angiotensin-converting enzyme (ACE) gene has been considered as a risk factor for IgA nephropathy and for its progression to end-stage renal failure. However, results from various studies are conflicting. We had genotyped the ACE gene in 100 patients with IgA nephropathy, 32 of whom were in end-stage renal failure and in 90 normal adult subjects. All DD cases were subjected to confirmation with a second PCR, performed with the insert-specific forward primer. Similar genotype frequencies were obtained for the 90 normal control subjects (II: 47%, ID: 44%, DD: 9%); for the 68 patients not in end-stage renal failure (ESRF) (II: 47%, ID: 46%, DD: 7%) and for the 32 patients with ESRF (II: 53%, ID: 38%, DD: 9%). The genotype frequencies in all 3 series are in Hardy-Weinberg equilibrium. These results suggest that ACE gene polymorphism is not a risk factor for IgA nephropathy and is not a predictor for its progression. Definitive proof of association between ACE gene polymorphism and progression in IgA nephropathy will require a prospective study, controlled for important risk factors, with adequate patient numbers and facility for confirming DD genotypes.

The course of pregnancy in a patient with nail-patella syndrome.

INTRODUCTION: The nail-patella syndrome is a rare autosomal dominant condition with high penetrance. Pregnancy in such a patient is rare and we believe this to be the first report of a live birth occurring in a patient with nail-patella syndrome. CLINICAL PICTURE: A 25-year-old patient presented in her first pregnancy with nephrotic syndrome associated with characteristic bone abnormalities and nail dysplasia and was later diagnosed to have nail-patella syndrome. In her second pregnancy, the course of her pregnancy was complicated by further deterioration of renal function with superimposed pre-eclampsia resulting in early delivery at 28 weeks. CONCLUSION: Such pregnancies should be regarded as high risk and managed jointly with the renal physician in a tertiary care centre to ensure an optimal outcome to the mother and baby.

Nail-patella syndrome and IgA nephropathy in a Chinese woman.

Nail-patella syndrome (NPS), also known as hereditary onycho-osteodysplasia, is an autosomal dominant pleiotropic disorder characterized by nailbed dysplasia or hypoplasia, absent or hypoplastic patellae, iliac horns and deformation or luxation of the radial head. Nephropathy is a known serious complication associated with NPS. In this report, we describe an adult Chinese woman with the clinical and radiological features of NPS who presented with the nephrotic syndrome. Renal biopsy disclosed focal segmental glomerulosclerosis on light microscopy, while immunofluorescence revealed predominant staining for IgA in the glomerular mesangium and along some capillary walls. Ultrastructural study confirmed the presence of paramesangial deposits as well as subendothelial collagen fibrils in the glomeruli. The histological findings were those of combined NPS and IgA disease, an association which has rarely been described.

Outcome of tunnelled central venous haemodialysis catheters inserted by radiologists.

Radiologists have only recently been involved in the percutaneous placement of tunnelled central venous haemodialysis catheters. We report our initial experience with our first 60 catheters. All catheters were successfully inserted. Immediate complications encountered included puncture site haemorrhage in 3 patients (5%) and puncture of the left brachiocephalic vein in 1 patient (1.7%). These were managed conservatively without any clinical sequelae. About 80% of the catheters were uncomplicated and removed electively. Slightly more than 80% of the catheters were in place for more than 30 days. Infection and blocked catheters were the most common short-term complications. Ten catheters (17%) were infected resulting in premature removal of 9. There was 1 death from presumed line sepsis. Mean duration before the onset of infection was 53 days; the rate of infection was 0.28 episodes per 100 catheter days. Five catheters (8%) were blocked or had poor flow. The mean duration before the onset of blockage was 39 days and the rate of blockage was 0.14 episodes per 100 catheter days. A higher proportion of catheters inserted from the left encountered complications. In conclusion, percutaneous insertion of tunnelled haemodialysis catheters by radiologists is safe and effective. The right internal jugular vein should be the preferred access site. Precautions should be taken to avoid infectious complications given the high rate of catheter removal amongst infected catheters.

Partial sequence analysis of the hepatitis C viral genome in Singapore patients.

The distribution of hepatitis C viral (HCV) genotypes in Singapore has not been previously determined. We studied the sera of 40 Singapore patients which were PCR-positive for HCV. The HCV genotypes were determined by direct sequencing of amplified sequences of the 5' non-coding region, after reverse transcription. Of the 40 samples, 35/40 (87.5%) were of HCV type 1, 2/40 (5.0%) were of type 2 and 3/40 (7.5%) were of type 3. The most common HCV genotype in this study was the type 1 genotype. Our results confirm the wide geographical distribution of HCV genotypes.

Comparative effects of arginine vasopressin and oxytocin in cell culture systems.

Arginine vasopressin (AVP) and oxytocin (OXT) induced contraction in cultured vascular smooth muscle cells (VSMC) and glomerular mesangial cells (GMC). The contractile response of AVP and OXT was paralleled by Ca2+ mobilization as assessed by 45Ca2+ efflux in a dose-dependent manner. The effects of AVP were blocked by pretreating VSMC and GMC with a V1 antagonist. OXT-stimulated effects, however, were not affected by preexposure of VSMC and GMC to an OXT antagonist but were inhibited by the V1 antagonist. Competition studies demonstrated displacement of [3H]AVP from its receptors by unlabeled AVP, the V1 antagonist, and high doses of OXT. The OXT antagonist was the least effective in displacing [3H]AVP. Thus occupancy of the V1 receptor by OXT may initiate signal transduction and contraction in VSMC and GMC in a manner qualitatively similar to that of the AVP agonist. Cultured myometrium cells (MMC) also contracted in response to AVP and OXT. Moreover, 45Ca2+ efflux increased in response to both hormones in a dose-dependent manner. AVP-stimulated contraction and 45Ca2+ efflux were blocked in MMC by pretreatment with V1 antagonist. OXT-induced effects were inhibited by the OXT antagonist but not by the V1 antagonist. Binding experiments showed that [3H]AVP was displaced equally by unlabeled AVP and V1 antagonist. Very high concentrations of OXT antagonist also demonstrated displacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary tuberculous chancre in a renal transplant patient.

A case of primary tuberculous chancre of the vulva is reported. Although a tuberculous infection in an immunocompromised patient is not uncommon, this is the first report of a primary tuberculous infection on the external genitalia in such a patient. The source of infection in this patient could not be determined.

Maintenance haemodialysis in Singapore.

The chronic haemodialysis programme of the Singapore General Hospital started in 1968 as a hospital-based fully nurse-assisted programme. This has since expanded to include Self Dialysis and Home Dialysis programmes. Data of 425 patients who entered the dialysis programmes was analysed retrospectively. The major cause of end stage renal failure was chronic glomerulonephritis (52%). Almost half of the patients in the haemodialysis programme were patients on self-dialysis (49%). There were 157 withdrawals and 116 deaths. Survival has improved tremendously with the use of treated water for dialysis from 1981. The 5 year survival in an earlier group of patients dialysed with untreated water was 48% compared with 81% in a late group dialysed with treated water (p less than 0.001). The pattern of complications has also changed with a lower incidence of dialysis osteomalacia, hypertension, hepatitis and eradication of dialysis dementia.

Hepatitis B vaccination in chronic renal failure patients undergoing haemodialysis: the immunogenicity of an increased dose of a recombinant DNA hepatitis B vaccine.

Thirty-two patients with end stage renal failure who were on haemodialysis and who had no previous exposure to hepatitis B virus were given four intramuscular injections of 40 micrograms (twice the recommended dose) recombinant DNA hepatitis B vaccine (Engerix B, Smith Kline Biologicals) at 0, 1, 2 and 6 months to determine the immunogenicity of this increased vaccine dose. The ages of these patients ranged from 23-54 years with a mean age of 40 years. There were 11 males and 21 females. Three patients underwent renal transplantation during the course of the study and were assessed separately. Antibody levels above 10 IU/L were noticed in 83% of the remaining 29 patients two months after the final dose with an anti-HBs geometric mean titre (GMT) of 2551 IU/L. The antibody response was 82% four months later although the GMT has fallen to 664 IU/L. Renal transplantation did not appear to affect the anti-HBs response to the above vaccination regime. None of the volunteers developed hepatitis B during the study. Our results were much better than results obtained in studies using twice the recommended doses given three times.

Gastroduodenal mucosa in uraemia: endoscopic and histological correlation and prevalence of helicobacter-like organisms.

This study aimed to determine the prevalence of endoscopic and histological gastroduodenitis as well as helicobacter-like organisms in patients with end stage renal failure undergoing maintenance dialysis treatment. A total of 322 out of 422 patients in our dialysis programme underwent endoscopy and gastroduodenal biopsy specimens were taken from 260. Endoscopic gastroduodenitis occurred in 158 (49%). Histological gastritis occurred in the gastric body or antrum in 134 patients (52%) and duodenitis in 52 (21%). There was no correlation between endoscopic and histological gastritis in contrast to a significant correlation for duodenitis. Helicobacter-like organisms occurred in the body or antrum in 81 (31%). Their presence was associated with gastritis--in particular acute and acute on chronic gastritis rather than chronic gastritis. Patients with gastritis were significantly older than those without (p less than 0.001) and had lower basal and peak acid outputs.

Erosive prepyloric changes in patients with end-stage renal failure undergoing maintenance dialysis treatment.

We endoscoped 322 of 422 patients with end-stage renal failure undergoing maintenance dialysis treatment to determine the prevalence of erosive prepyloric changes (EPC) in uraemia. EPC grade 1 was found in 79 patients (25%), grade 2 in 16 (5%), and grade 3 in 43 (13%). EPC grades 2 and 3 were commoner among uraemic patients than among non-uraemic patients presenting for gastroduodenoscopy (13 of 198 = 6%; p less than 0.001). Patients with EPC grades 2 and 3 were older, had been receiving dialysis longer, and were more likely to be receiving haemodialysis rather than peritoneal dialysis when compared with patients without EPC. Histologic gastritis of the body and antrum was less common among patients with EPC grades 2 and 3 than among patients without EPC. The prevalence of Campylobacter-like organisms was similar in patients with and without EPC.