Charles van Ypersele de Strihou

Low molecular weight proteinuria in human immunodeficiency virus-infected patients

To determine whether human immunodeficiency virus (HIV) infection is associated with incipient tubular or glomerular defects, we determined the urinary excretion of four low molecular weight proteins (LMWP); beta2-microglobulin (U-beta2-m), cystatin C (U-cyst C), Clara cell protein (U-CC16), and retinol-binding protein (U-RBP), the markers of tubular dysfunction, the excretion of albumin (U-Alb), a marker of glomerular defect, and the excretion of N-acetyl-beta-D-glucosaminidase (U-NAG), a marker of structural damage of the proximal tubular epithelium. Their determinants have been assessed by stepwise regression analysis using as possible predictors age, sex, serum-beta2-m (S-beta2-m), CD4 lymphocyte count, or HIV infection stage and therapy. The study involved 76 HIV-infected patients without renal disease, 56 with S-beta2-m < 5 mg/L (Group B1), 20 with S-beta2-m > or = 5 mg/L (Group B2), and 30 HIV-negative controls. Fourteen patients (18.4%) had no abnormal urinary protein loss, and 62 (81.6%) had elevated urinary excretion of at least one protein (Alb, LMWP, or NAG). A single urinary protein was abnormal in 21 patients (U-beta2-m, n = 9; U-RBP, n = 2; U-CC16, n = 4; and U-Alb, n = 6). At least two LMWP were abnormal without increased U-Alb in 23 patients (12 with increased and 11 with normal U-NAG). Ten patients had an increased urinary excretion of at least one LMWP together with U-Alb (5 with increased and 5 with normal U-NAG). An increased urinary excretion of all proteins was observed in the last 8 patients. The average urinary excretion of all proteins (except cyst C) was significantly higher in HIV than in the control group. As expected, U-beta2-m and the prevalence of abnormal U-beta2-m values were higher in the B2 than in the B1 group (P = 0.0001), whereas the average urinary excretion and the prevalence of elevated values of Alb, LMWP (except beta2-m) or NAG were the same in both HIV groups. By stepwise regression analysis, age emerged as a significant determinant of urinary excretion of beta2-m and CC16, whereas male sex was associated with increased U-CC16. S-beta2-m, CD4-lymphocyte count, or HIV infection stage emerged as significant determinants only for U-beta2-m as a consequence of a close correlation between S-beta2-m and either HIV infection stage (r = -0.52, P = 0.0001), or CD4 count (r = -0.45, P = 0.0002). Over 80% of HIV-infected patients without overt renal disease have evidence of glomerular permeability defects or tubular dysfunction, whatever the stage of the disease. U-Alb, RBP, and CC16 appear as the most sensitive and reliable early markers of these abnormalities. Their cause and prognostic value remain to be determined.

Renal Side-effects of Nonsteroidal Antiinflammatory Drugs - Clinical Relevance

Nonsteroidal antiinflammatory drugs (NSAIDs) induce a variety of renal side effects. We review their prevalence and clinical relevance, and identify the patients who are most at risk for these complications. NSAIDs induce hemodynamic renal failure in states of compromised renal perfusion and in the presence of a preexisting nephropathy. Association of triamterene and indomethacin is especially nephrotoxic and should be avoided. NSAIDs cause sodium retention and impair the natriuretic effect of diuretics: this side effect is clinically relevant in edema-forming states. Hyperkalemia induced by NSAIDs is harmful in case of renal failure and hypoaldosteronism. NSAIDs may induce an acute interstitial nephritis often associated with the nephrotic syndrome; the event is rare and unpredictable, and mainly propionic acid derivatives have been incriminated. NSAIDs are reported to attenuate the hypotensive effect of various drugs; further studies are warranted to better delineate the clinical relevance of this observation.

Late Urinary-tract Infection After Transplantation - Prevalence, Predisposition and Morbidity

We have evaluated the incidence, prevalence, predisposing factors and evolution of urinary tract infection (UTI) developing late after transplantation in 63 patients whose graft had lasted at least 3 months and whose follow-up averaged 7 years. Beyond 3 months after transplantation incidence of UTI decreases progressively, from 25 to 0%, 50% of the patients remaining free of infection throughout the period of observation. Neither the original kidney disease except perhaps diabetic nephropathy nor the presence of vesicoureteral reflux were predisposing factors. Incidence and prevalence in females were twice that in male. Late UTI did not affect graft or patient survival, or graft function at 5 years. Most UTI were asymptomatic and had a benign course. However, in 3 patients septicemia or graft dysfunction ensued demonstrating the need for continuous monitoring of urine cultures.

Beechnuts and outbreaks of nephropathia epidemica (NE): of mast, mice and men

Hantavirus Reference Centre, Laboratory of Clinical Virology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedestraat, 10, 3000 Leuven, Belgium, Nephrology, Catholic University of Louvain, Avenue Hippocrate, 1200 Brussels, Belgium, Virology Unit, Institute of Tropical Medicine, Nationale Straat, 155, 2000 Antwerp, Belgium and M3-BIORES, Biosystems Department, Katholieke Universiteit Leuven, Willem de Croylaan 34, 3001 Leuven, Belgium

β2-Microglobulin Amyloidosis in a Patient Treated Exclusively by Continuous Ambulatory Peritoneal Dialysis

The histological demonstration of beta 2-microglobulin (B2M) amyloidosis in a 75-year-old man treated exclusively by continuous ambulatory peritoneal dialysis (CAPD) for 87 months is reported. Amyloid deposits were detected in all joints from which synovial specimens were obtained at autopsy. It is of note that the patient had never undergone hemodialysis and had suffered only one episode of peritonitis. Both features are of interest, as the few reports of dialysis-related amyloidosis (DRA) in CAPD include patients who have been hemodialyzed and have suffered repeated episodes of peritonitis, both conditions being incriminated in the genesis of B2M amyloidosis. We conclude that DRA may develop in the absence of artificial membranes or frequent peritonitis episodes.

Beta-2-microglobulin amyloidosis

The first report of the carpal tunnel syndrome (CTS) in hemodialysis (HD) patients was published in 1975 (1). Five years later Assenat et al. reported that amyloid was present in tissue harvested during CTS surgery in HD patients (2). In 1985 Gejyo et al. identified β2-microglobulin (β2m) as the main constituent of “dialysis-related” amyloid deposits (3), a complication hence named β2-microglobulin amyloidosis, now abbreviated as Aβ2m in accordance with WHO guidelines on the nomenclature of amyloidosis (4). The subsequent 10–12 years were mainly devoted to the elucidation of the determinants of β2m metabolism in renal failure and dialysis, as well as to the careful delineation of the clinical picture, epidemiology, pathology and diagnosis of Aβ2m (5— 10). The beneficial influence of renal transplantation on Aβ2m was also reported (11,12). Over the past 5— 7 years emphasis has been put on more fundamental aspects of the amyloidogenic process (13–15).

Site of action of torasemide in man

SummaryThe effect of torasemide, a new orally and parenterally active diuretic agent, on the renal mechanisms of dilution and concentration was studied in 6 healthy volunteers. The experimental conditions included water and osmotic diuresis. Torasemide caused maximal chloruresis and natriuresis during the 20–40 min after administration. The effect was more pronounced under osmotic diuresis and persisted throughout the 100 min of those experiments. A distinct effect both on free water clearance (

Reduction of albuminuria by angiotensin receptor blocker beyond blood pressure lowering: Evaluation in megsin/receptor for advanced glycation end products/inducible nitric oxide synthase triple transgenic diabetic nephropathy mouse model

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