Lipoprotein glomerulopathy: first case in a white European

Since 1988, 11 cases of a new entity, ‘Lipoprotein glomerulopathy’(LG), were described in Japan. Some of these reports suggestedthat this glomeruler lipid storage is due to excess apo E associatedwith heterozygous E2/3 apo E isoform. We report the first caseof LG in a white European with no such lipid abnormalities.Proteinuria was discovered in 1967 when he was 42. Blood pressureand renal function were normal. Family history was negative.Renal biopsy disclosed lesions which were only understood atthe time of the Japanese publications. They were composed ofendocapillary glomerular deposits. Staining for lipids disclosedcapillary loop obstruction with lipid droplets. Electron microscopyshowed confluent droplets of various sizes obstructing capillaryloops. Proteinuria progressively increased. In 1974 repeat renalbiopsy showed the same lipid deposits, now associated with focal-segmentalglomerulo-sclerosis (FSGS). Several serum lipoprotein and apolipoproteinstudies ruled out any specific lipid derangement. This suggesteda local glomerular disorder, presumably affecting the glomerularendocapillary disposal of lipids. A third biopsy showed progressiveglomerular destruction by FSGS with persistence of the lipiddroplets. Renal insufficiency progressed and haemodialysis wasstarted in 1992. This observation suggests that LG is a localglomerular, not a general lipid disorder and indicates thatthis disease is not restricted to Asian patients.     

Pharmacokinetics of rilmenidine in patients with chronic renal insufficiency and in hemodialysis patients

The pharmacokinetics of rilmenidine (1 mg orally) was studied in 3 groups of patients with stable chronic renal insufficiency. This was an open, single-blind study following a single administration, and after 15 days of treatment. Group 1 included 11 patients with a creatinine clearance between 15 and 80 mL/min. Group 2 included 17 patients with a creatinine clearance <15 mL/min. Group III included 10 hemodialysis patients. In patients with chronic renal failure, total plasma clearance and renal clearance of rilmenidine decreased; terminal half-life was 30–42 hours, which is clearly longer than previous values achieved in healthy volunteers. After repeated administration (1 mg daily in group 1, 1 mg every other day in group 2, 1 mg at the end of each dialysis session in group 3), the area under the curve was significantly increased, corresponding to drug accumulation. The steady state was reached after 6 days in patients in group 1 and after 8 days in patients in group 2. The pharmacokinetics of rilmenidine was linear since the terminal elimination half-life and renal clearance were not significantly different after single and repeated administration of rilmenidine. A positive correlation was found between rilmenidine total plasma clearance and creatinine clearance, and between rilmenidine renal clearance and creatinine clearance. Mean rilmenidine hemodialysance was 85 mL/min, that is, 26% of the rilmenidine renal clearance value achieved in healthy volunteers (330 mL/min). Thus, the following dosage schedule can be proposed. In patients whose creatinine clearance ranges between 15 and 80 mL/min, a 1 mg dose every day can be recommended. In patients whose creatinine clearance is <15 mL/min, a 1 mg dose every other day can be recommended. Because of a nonsignificant hemodialysance, an additional dose at the end of a 4-hour hemodialysis session is not required. In patients undergoing regular hemodialysis, on the basis of 3 4-hour sessions a week, a 1 mg dosage at the end of each dialysis session seems appropriate.     

Insulin Responses to Glucose and Secretin in Uraemic and Normal Subjects

Abstract. Insulin secretion was studied in two groups of subjects: controls and uraemic patients on maintenance haemodialysis. Two procedures were used: 1) four rapid glucose injections before, during and after an infusion of glucose 2) five injections of secretin at varying time intervals. The system of two functional insulin pools, as first described in normal man by Porte and Bagdade [1] is also observed in uraemic subjects. Basal insulin level is increased and glucose tolerance impaired in this group. Insulin secretion from the two pools is higher when insulin plasma levels are expressed as absolute values but becomes lower when relative values calculated as per cent of the base line are considered. Thus uraemia may be considered as associating insulin antagonism and resistance to relatively defective insulin secretion.     

Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome : workshop recommendations

Management of idiopathic glomerular disease associated with nephrotic syndrome (INS) remains controversial and one of the most complex areas relates to utilization of the drug cyclosporin. This is despite its demonstrated effectiveness in several histologic types of the INS in randomized controlled trials. Cyclosporin is effective in inducing remission of proteinuria in approximately 80% of steroid-sensitive cases of minimal change disease (MCD). Cyclosporin is also effective in both the induction of remission and long-term preservation of renal function in steroid-dependent/-resistant MCD and steroid-resistant focal segmental glomerulosclerosis (FSGS). The overall response rate in FSGS is lower than in MCD, and long-term therapy (>12 months) may be required to both achieve remission and sustain it. Cyclosporin therapy is also of benefit in reducing proteinuria in 70-80% of patients with steroid-resistant membranous nephropathy (MGN). In MGN, the maximum benefit is often delayed compared to MCD (>12 weeks). Cyclosporin is generally well tolerated and safe. The major concern remains the nephrotoxicity, but with careful monitoring of the patient's renal function; minimizing the maintenance dose and utilizing repeat renal biopsy in those receiving long-term therapy, this risk can be minimized. The algorithms have been developed derived from the best evidence in the literature in each of the histologic types to help provide a guide to the integration of cyclosporin into the management of INS for the practicing nephrologist.