Collagenofibrotic glomerulopathy- report of a rare renal disease with serial biopsies.

INTRODUCTION: Collagenofibrotic glomerulopathy or collagen type-III glomerulopathy is a rare glomerular disease characterised by the deposition of type III collagen fibres in the subendothelial space and mesangium of the glomerulus. CASE REPORT: Here, we present a case of collagenofibrotic glomerulopathy in a 49-year-old Indian female, the first to be reported from Singapore. Renal biopsy showed PAS (periodic acid-Schiff), silver and Congo red negative, amorphous extracellular material that expanded mesangial and subendothelial regions. Such materials were strongly positive for anti-collagen III immunofluorescent staining. Under electron microscopy, the mesangial and some subendothelial regions were greatly expanded by abundant collagen fibres which were different from normal collagen III fibres in both appearance and periodicity. DISCUSSION: The availability of past renal biopsies for reference offered insight into disease progression. From the initial diagnosis of focal segmental glomerulosclerosis to eventually collagenofibrotic glomerulopathy over a time span of more than 10 years, this case highlights the gradual accumulation of collagen fibres in the glomeruli before classical features are apparent. It also emphasises the importance of electron microscopy in the diagnosis of this disease.

Epstein-Barr virus-associated T-cell lymphoma in solid organ transplant recipients.

Post-transplantation lymphoproliferative diseases (PTLDs) are a heterogenous group of lymphoid proliferative disorders occurring in transplant patients. Most PTLDs are B-cell in origin; T-cell PTLDs are seldom reported, and EBV-associated T-cell PTLDs are rare. The first case of a T-cell, non-EBV-associated PTLD was first described in a renal allograft recipient in 1987. A total of 40 cases of T-cell PTLDs in solid organ transplant recipients have been reported. However, so far only 16 cases of EBV-associated T-cell PTLDs have been reported in the literature. The sites of occurrence of EBV-associated T-cell PTLDs were in the gastrointestinal tract, lungs, bone marrow, skin, liver and spleen. The pathogenesis of EBV-associated T-cell PTLD is uncertain; it is speculated that the EBV may infect a subset of T-cells that express the CD21 receptor. The present treatment of EBV-associated T-cell PTLD consists of surgical removal, reduction or withdrawal of immunosuppression and/or radiotherapy and chemotherapy. The prognosis is uncertain, and the 1-year survival for patients who were followed up for 1 year was 50%.

Acute renal failure from hemoglobinuric and interstitial nephritis secondary to iodine and mefenamic acid.

Mefenamic acid ingestion, usually in excess and over prolonged period is known to produce interstitial nephritis, or less commonly papillary necrosis, with acute renal failure. However, it is not dose-dependent for the induction of tubulointerstitial damage. Excess iodine ingestion is known to produce toxicity and possible death, but acute renal failure is rare. There is evidence from clinical and experimental data that iodine has toxic effect on tubular epithelial cells. Iodine has not been documented to produce red cell hemolysis and hemoglobinuria. We present a unique case of acute renal failure from hemoglobinuric and acute interstitial nephritis secondary to suicidal ingestion of potassium iodide solution and also ingestion of a few mefenamic acid tablets. These agents led to potentiation of the renal injury from hemoglobinuric tubulopathy, probably from the iodine, and renal dysfunction from alteration of renal perfusion by selective COX-1 inhibition of prostaglandin production, and induction of acute interstitial nephritis from mefenamic acid, leading to acute renal failure which was reversible by hemodialysis and supportive therapy.

Once-daily intraperitoneal gentamicin is effective therapy for gram-negative CAPD peritonitis.

OBJECTIVE: To report our 3-year experience with the use of once-daily intraperitoneal (IP) gentamicin in the treatment of gram-negative continuous ambulatory peritoneal dialysis (CAPD) peritonitis. DESIGN: A prospective cohort study in prevalent CAPD patients. SETTING: A tertiary care institution. PATIENTS: All CAPD patients who presented with new episodes of peritonitis were studied. At presentation with peritonitis, IP vancomycin and gentamicin were administered as empirical therapy. IP gentamicin was given at a single daily dose of 40 mg/2 L in the overnight bag. The antimicrobial agents were reviewed when the culture results became available. Intraperitoneal ceftazidime was added for the treatment of pseudomonas peritonitis. MAIN OUTCOME MEASURES: Results of microbiological cultures and clinical outcomes of peritonitis were analyzed. RESULTS: Over a 36-month period, 190 episodes of peritonitis were recorded, of which 62/190 episodes (32.6%) isolated gram-negative organisms. The gram-negative organisms isolated were Escherichia coli, 15/62 episodes (24.1%); Pseudomonas aeruginosa, 12/62 episodes (19.4%); Acinetobacter spp, 12/62 episodes (19.4%); Klebsiella spp, 10/62 episodes (16.1%); and others, 13/62 episodes (21.0%). The overall treatment success rate was 66.1%. The treatment success rates were 74.0% if pseudomonas infections were excluded, 76.1% if gentamicin-resistant pathogens were excluded, and 80.5% if both pseudomonas infections and gentamicin-resistant pathogens were excluded. CONCLUSIONS: Once-daily IP gentamicin appears to be effective in the treatment of gram-negative CAPD peritonitis.

Peptic ulcer and gastritis in uraemia, with particular reference to the effect of Helicobacter pylori infection.

AIMS: To determine: (i) the prevalence of histological gastritis and peptic ulcer; and (ii) the clinical features of peptic ulcer, in patients with end-stage renal failure. METHODS: Upper endoscopy was performed by a single observer in 268 patients with end-stage renal failure over a 6-year period. Gastric histology and Helicobacter pylori status were studied in 40 consecutive subjects in whom there were no contraindications for gastric biopsy and who had not used antibacterial drugs in the preceding 4 weeks. As there are only limited data for healthy volunteers in Singapore, 33 age-, sex- and race-matched patients with functional dyspepsia from an earlier drug trial and 18 healthy volunteers who were not age-matched were used as controls. The clinical features of 43 consecutive uraemic patients with peptic ulcer were compared with those of 118 consecutive non-uraemic peptic ulcer patients seen by the same author. RESULTS: Among uraemic patients, histological gastritis was less common, compared with healthy volunteers and functional dyspepsia patients. Helicobacter pylori infection as assessed by histology was also less common among uraemic patients compared with functional dyspepsia patients, but the difference was not statistically significant on serological assessment. Uraemic patients with ulcer had an equal sex ratio, in contrast to a male preponderance among peptic ulcer patients with normal renal function. Uraemic patients with ulcer were more likely to be pain-free, to present with haemorrhage, to have multiple ulcers and postbulbar duodenal ulcers, but were less likely to have H. pylori infection. Among uraemic subjects, the prevalence of H. pylori infection was similar whether or not peptic ulcer was present. CONCLUSIONS: The prevalence of histological gastritis was lower in uraemic patients when compared with patients with functional dyspepsia and healthy volunteers. Peptic ulcers in uraemic subjects have different clinical characteristics from peptic ulcer in non-uraemic subjects.

Psychosocial and psychiatric morbidity in patients on CAPD.

Continuous ambulatory peritoneal dialysis (CAPD) is an important mode of therapy for patients with end-stage renal disease. Although techniques and patient survival rates have improved, the psychosocial rehabilitation of Asian CAPD patients has not been studied. The aim of this study is to measure the extent of psychosocial and psychiatric morbidity in a sample of Asian CAPD patients. Patients from the outpatient CAPD facility affiliated with a tertiary care hospital were randomly selected and enrolled in the study. Demographic and clinical data were collected. Psychosocial and psychiatric assessments using the Hospital Anxiety and Depression Scale and coping style questionnaires were performed by a trained psychiatrist. The patients' most bother-some symptoms and specific worries were noted. Thirty of 105 stable CAPD patients (mean age 54.2 +/- 14.1 years, M:F 1:2, mean duration on CAPD 22.3 +/- 8.3 months) were studied. Twenty-one patients were married. Twenty-two patients were uneducated, 19 were unemployed, and 9 were homemakers. Based on the Hospital Anxiety and Depression scales, 50% of the patients were identified as cases of anxiety and 13% as depression. Although 93% of the patients accepted their illness, 46% of the patients were in a state of despair and hopelessness. Pruritus was the most frequent complaint (40%), followed by dietary restrictions (23%). The main worries were financial in 83% of patients, sexual dysfunction in 73%, and unemployment in 67%. In conclusion, Asian CAPD patients have a high degree of undetected psychosocial and psychiatric morbidity. These issues need to be addressed to provide adequate psychosocial rehabilitation.

Paracetamol and its metabolites in saliva and plasma in chronic dialysis patients.

1. Many pharmacokinetic studies on paracetamol are based on saliva paracetamol concentrations. The utility of saliva in patients with chronic renal failure is unclear. In this study, concentrations of saliva and plasma paracetamol and its major metabolites, sulphate and glucuronide conjugates were determined at 0.5, 1, 2 and 3 h after the ingestion of 1 g paracetamol in 20 patients with endstage renal failure. Ten haemodialysis patients were studied on a non-haemodialysis day and during a haemodialysis session. The other 10 patients were on chronic ambulatory peritoneal dialysis. 2. The plasma paracetamol concentrations attained in all groups were not different from those reported previously in healthy subjects. Mean +/- s.d. plasma paracetamol concentrations at 0.5 h in haemodialysis patients on a non-haemodialysis day, during haemodialysis and in those on chronic ambulatory peritoneal dialysis were 15.3 +/- 8.2, 21.5 +/- 10.9 and 18.2 +/- 12.3 micrograms ml-1 respectively. 3. The saliva paracetamol concentrations were highly variable and unpredictable. Saliva paracetamol concentrations at 1, 2 and 3 h after ingestion in the haemodialysis group during haemodialysis were 31.5 +/- 20.1, 14.1 +/- 10.4 and 7.3 +/- 3.8 micrograms ml-1 respectively, significantly (P < 0.05; paired t-test) higher than the corresponding plasma paracetamol concentrations which were 11.0 +/- 2.8, 6.5 +/- 2.8 and 3.2 +/- 0.9 micrograms ml-1 respectively. 4. Correlation coefficients between saliva and plasma paracetamol concentrations in haemodialysis patients on a non-haemodialysis day and during haemodialysis and in chronic ambulatory peritoneal dialysis patients were poor; r = 0.58 (P < 0.0002); r = 0.40 (P < 0.02); and r = 0.13 (P = 0.49) respectively. 5. Three hours after paracetamol ingestion, plasma paracetamol, sulphate and glucuronide concentrations were significantly (P < 0.05) reduced in haemodialysis patients during haemodialysis when compared with the same patients on a non-haemodialysis day (paired t-test) and to the chronic ambulatory peritoneal dialysis group (Kruskal-Wallis ANOVA) except for plasma glucuronide. This indicates the effective removal of paracetamol and metabolites by haemodialysis. In contrast, chronic ambulatory peritoneal dialysis seemed to remove glucuronide only. 6. In the light of the poor correlation between saliva and plasma paracetamol in dialysis patients in this study, we would like to caution against using saliva paracetamol concentrations for pharmacokinetic studies in this group of patients.

Transplant renal artery stenosis presenting with recurrent acute pulmonary edema.

Renal artery stenosis of the transplant kidney occurs in approximately 6% of renal allograft recipients. Severe bilateral renal artery stenosis and unilateral renal artery stenosis to a single functioning kidney have been described as causes of recurrent pulmonary edema in nontransplant patients with normal cardiac function. We report 2 patients with severe transplant renal artery stenosis who presented with recurrent episodes of acute pulmonary edema. Successful revascularization in 1 patient prevented the recurrence of pulmonary edema. In renal allograft recipients who present with unexplained recurrent episodes of acute pulmonary edema, who do not have an obvious cardiac cause, transplant renal artery stenosis should be considered as a possible etiology.

A prospective randomized comparison of the Swan neck, coiled, and straight Tenckhoff catheters in patients on CAPD.

Our objective was to study the impact of peritoneal catheter configuration on continuous ambulatory peritoneal dialysis (CAPD)-related infections, mechanical complications, and patient dropout in a prospective randomized trial. Forty consecutive patients who were commencing CAPD were randomized to receive either a double-cuff, Swan neck coiled catheter or a double-cuff, straight Tenckhoff catheter, implanted by surgical technique. There was no significant difference in the peritonitis rate between the two groups. There was a lower rate of exit-site infection in the Swan neck group compared to the straight catheter group (0.29 vs 0.60 episodes/patient-year, p < 0.05). Catheter-tip migration occurred in 3 patients with the straight catheters compared to one patient with the Swan neck catheter. No patient had to discontinue CAPD because of mechanical complications. The number of CAPD patient dropouts was not significantly different between the two groups. The Swan neck configuration resulted in a significant reduction in the rate of exit-site infections. The coiled component of the catheter may lead to fewer episodes of catheter-tip migration. However, catheter configuration did not influence the number of technique failures.

Acute cyclosporine A nephrotoxicity in a renal allograft recipient with hypothyroidism.

Cyclosporine A (CsA) is an important immunosuppressant in kidney transplantation. Acute CsA nephrotoxicity secondary to high drug levels is a well-recognized complication in the immediate posttransplant period. Cyclosporine A is metabolized in the body by the hepatic cytochrome P-450 enzyme system. We present a case of a hypothyroid patient who developed toxic blood CsA levels and acute nephrotoxicity with standard doses of CsA. A reduction of CsA levels led to an improvement of allograft function. Correction of the hypothyroid state resulted in the normalization of CsA requirements, but overcorrection led to an increased requirement of CsA. Thyroid dysfunction should be considered as an interacting factor in the metabolism of CsA.

Lipoprotein (a) levels and clinical correlations in CAPD patients.

Dyslipidemia is an important risk factor for atherosclerotic vascular disease. Serum lipoprotein (a) [Lp(a)] has been implicated as an independent atherogenic risk factor. We measured serum (Lp(a) levels in our patients and studied its correlations with other lipoproteins and clinical parameters. All stable patients on continuous ambulatory peritoneal dialysis (CAPD) for more than one month were enrolled in the study. Fasting serum Lp(a), total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, apolipoprotein-A and apolipoprotein-B levels were measured on entering the CAPD program and at 3 monthly intervals. One hundred and nine patients (M/F: 65/44, mean age +/- SD: 59.5 +/- 12.0 years) were studied. Fifty-two patients had diabetes mellitus. Age- and sex-matched normals were used as controls. Serum Lp(a) levels were raised in 54.5% of CAPD patients compared to 18.6% of controls (p < 0.01). There was no significant change in Lp(a) levels over time. Serum Lp(a) levels showed positive and negative correlations with LDL-cholesterol and triglycerides, respectively, but not with age, sex, diabetic status, and serum total cholesterol and albumin levels. Thirty-six of 54 (66.7%) patients with serum Lp(a) levels greater than 30 mg/dL had either coronary, cerebral, and/or peripheral vascular disease compared to 30/55 (54.5%) of patients with serum Lp(a) levels less than 30 mg/dL (p = NS). In conclusion, serum Lp(a) levels were raised in a significant proportion of CAPD patients, but there was no significant association with vascular disease.

A prospective randomized comparison of single versus multidose gentamicin in the treatment of CAPD peritonitis.

There is an increasing trend towards the use of aminoglycosides in a once-daily dose administration for the treatment of severe infections in nonrenal failure patients. The use of once-daily dose aminoglycoside therapy may be associated with a reduction in toxicity. We performed a prospective randomized study comparing once-daily versus multiple-dose gentamicin in the treatment of continuous ambulatory peritoneal dialysis (CAPD) peritonitis. Seventy-three patients with 100 new episodes of peritonitis were enrolled in the study. At presentation of peritonitis, the patients were alternately assigned to receive either intraperitoneal gentamicin at a dose of 40 mg/2 L dialysate administered as a once-daily dose or gentamicin at a dose of 10mg/2 L dialysate administered 4 times per day. All patients also received intraperitoneal vancomycin at a dose of 1 g per week. There were no significant differences in the treatment success (88% vs 82%, p = NS) and relapse (18% vs 20%, p = NS) rates between the once-daily dose and multiple-dose groups. The mean trough serum gentamicin level was higher in the once-daily dose group compared to the multiple-dose group (0.75 +/- 0.72 vs 1.50 +/- 1.40 mg/L). In conclusion, gentamicin administered in a once-daily dose is as effective as multiple-dose administration in the treatment of CAPD peritonitis. The lower gentamicin level with once-daily dose administration may be associated with a reduction in aminoglycoside toxicity.