Paul Michielsen

Silicon Nephropathy: a Possible Occupational Hazard

A 37-year-old white male, working in a tile factory, presented proteinuria with no obvious tubular dysfunctional. Renal biopsy disclosed a mild focal segmental proliferative glomerulonephritis. Distinct alterations were found by electron microscopy, especially in the proximal tubular cells. Because of a history of heavy dust exposure the silicon content was determined in the kidney biopsy tissue. The finding of 150 mg/kg silicon on tissue dry weight supports the diagnosis of silicon nephropathy.

Presumed consent to organ donation: 10 years' experience in Belgium.

More than 30 years after cadaver kidney transplantation became a routine clinical procedure, organ shortage is still limiting its application, and the role played by legislation in this shortage remains controversial. Unfortunately, partisans of the two sorts of law-informed consent and presumed consent-have often argued from prejudice rather than objective evaluation. Experience with a presumed consent law in Belgium illustrates that the matter is more complex than usually acknowledged. In this review I focus on how the new law affected organ retrieval and the factors that influenced its acceptance by all parties.

OESTROGEN CONTAINING ORAL CONTRACEPTIVES, DECREASED PROSTACYCLIN PRODUCTION, AND HAEMOLYTIC URAEMIC SYNDROME

Dr. Ylikorkala and colleagues (January 3, p. 42) present evidence for lowered (PGI2) prostacyclin production in normal women after prolonged use of estrogen-containing (OCs) oral contraceptives but not after use of a progestagen-only OC. We have seen a 23-year old multiparous normotensive woman whohad a (HUS) hemolytic uremic syndrome 5 months postpartum and 4 months after starting on a combined OC (Mestranol + chlormadinone acetate). HUS recurred 8 years later, 5 years after a successful cadaver kidney transplantation and 10 months after resumption of combined OC intake (thinyl estradiol levenorgestrel). In the interim, a progestagen-only OC (lynestrenol) was used without problems for 7 years. Other causes of HUS (systemic disease, malignant hypertension, transplant rejection, infection) were excluded. Details of this case will be published elsewhere. A disorder in PGI2 production has been proposed as the underlying basic abnormality in some patients with HUS. In the light of the observation of Ylikorkala et al, the recurrence of HUS in a transplanted kidney after resumption of an estrogen-containing OC could be seen as a confirmation of the role of PGI2 in HUS. HUS-related to OCs is rare is view of the large numbers of women on the pill; thus a genetically determined predisposition is likely. This is supported by the observation of HUS in adult sisters taking OCs. Further data are needed to discover if this predisposition is a dificient production of PGI2 as suggested by Remuzzi et al.

Protein-Losing Enteropathy in Systemic Lupus erythematosus

A 33-year-old woman presented a recurrent steroid-sensitive protein-losing enteropathy as the major manifestation of systemic lupus erythematosus. An increased capillary permeability for proteins is considered to be the most likely explanation.

Indomethacin and Platelet Aggregation in Chronic Glomerulonephritis: Existence of Non-responders

Indomethacin given to adults with glomerulonephritis usually reduces their urinary excretion of protein and fibrinogen/fibrin-related (F.R.) antigen. Nevertheless, non-responders exist. Platelet aggregation is significantly more strongly inhibited by indomethacin in good responders than in nonresponders. This supports the hypothesis that the reduction of urinary excretion of F.R. antigen during indomethacin administration is related, at least in part, to inhibition of intrarenal platelet aggregation and of the subsequent fibrin deposition.

Non-phenacetin analgesics and analgesic nephropathy Clinical assessment of high users from a case-control study [ ] *

BACKGROUND A recent large-scale case-control study on analgesic nephropathy (SAN) [1] found no increased risk of end-stage renal disease (ESRD) in users of combined or single formulations of phenacetin-free analgesics. In a subgroup of 22 high users, however, a dose-dependent increased risk was found, which raised the question if these patients presented or not with analgesic nephropathy (AN). METHODS The individual questionnaires of this subgroup of high users were reviewed, and the total lifetime intake of different types of analgesics was calculated. For evidence of AN, the following data were considered: (1) the amount and type of analgesics consumed, (2) the cause of ESRD, as diagnosed by the nephrologist in charge of the patient and (3) renal imaging and other relevant laboratory data. RESULTS This group of ESRD patients consumed on average 7.8 kg of antipyretic analgesics (range 30.8-2.7 kg) over an average of 21.5 years (range 35-6 years). Single analgesics were exclusively used by 12 patients (54.5%) and combined analgesics by 5 patients (22.7%), while 5 patients used both. None of the patients was diagnosed as having AN, and a review of the questionnaires did not disclose evidence suggestive of AN. The possibility that, irrespective of AN, the analgesic (ab)use contributed to the progression of existing renal diseases cannot be answered in the absence of well-defined criteria. The data supporting the existence of such an analgesic-associated nephropathy (AAN) are, however, not consistent and most likely due to confounding by indication. CONCLUSION In a group of ESRD patients with high use of non-phenacetin analgesics, no evidence of AN was found. There is no evidence that (ab)use of analgesics or NSAIDs other than phenacetin leads to a pathologically or clinically defined renal disease that could be named AN or AAN.

Evidence that stimulator cell-derived IL-6 and IL-1 are released in the mixed lymphocyte culture but are not requisite for responder T cell proliferation

We investigated whether IL-6 and (or) IL-1 are crucial costimulatory signals in the human MLC with purified responder T cells. With allogeneic PBMC as stimulators, IL-6 and IL-1 were rapidly produced, and reached plateau values of 100–300 U/ml and 200–500 pg/ml after 24 hr, respectively. Irradiated or mitomycin-c treated PBMC could easily be induced (with LPS) to produce IL-6 and IL-1 while no activity was measured after 48 hr in the supernatant of PHA-stimulated T cells, suggesting that in the MLC the monokines were entirely produced by stimulator PBMC. In cultures of responder T cells and stimulator B cells, no IL-6 and IL-1 activity was measured in the supernatant, and only a marginal proliferative response was found. Exogenous IL-6 and IL-1 increased in a dose-dependent way the B-cell-in-duced alloresponse and induced significant cytotoxicity in the responder cells. Antisera to IL-6 and IL-1 totally inhibited the induced response. The proliferation was accompanied by increased IL-2 production and IL-2R expression. Preincubation of B cells with IL-6 and IL-1 did not improve the proliferation, suggesting direct effects of IL-6 and IL-1 on the T cells. The proliferative responses induced by B cells and exogenous IL-6 and IL-1 represented a fraction of those induced by PBMC. Moreover, in PBMC-stimulated cultures exogenous IL-6 and IL-1 or antisera to these lymphokines did not significantly alter proliferative responses, cytotoxicity, IL-2 levels in the supernatant, or IL-2R expression on responder T cells. We conclude that a role for IL-6 and IL-1 in allogeneic T cell stimulation can be demonstrated in conditions of suboptimal stimulation with B cells. With PBMC, neutralizing antisera to these cytokines do not seem to inhibit the proliferative response, suggesting that these cells are superior in alloantigen presentation either by producing various costimulatory signals or by the fact that due to cell-cell contact stimulator cell-derived monokines cannot be blocked. This finding makes it unlikely that antimonokine therapy will be useful in transplantation.

Immunological and clinical observations in diabetic kidney graft recipients pretreated with total-lymphoid irradiation

In a feasibility study, twenty patients with end-stage diabetic nephropathy were treated with fractionated total-lymphoid irradiation (TLI, mean dose 25 Gy), before transplantation of a first cadaveric kidney. During radiotherapy, only one patient had a serious side effect (bone marrow depression). After transplantation four patients died (one of a myocardial infarction, one of ketoacidosis, and two of infections occurring during treatment of rejection crises). One graft was lost because of chronic rejection. The other 15 patients have a functioning graft (mean follow-up 24 months) and receive low-dose prednisone alone (<10 mg/day, n=ll) or in conjunction with cyclosporine (n=4) as maintenance immunosuppressive therapy. A favorable clinical outcome after TLI (no, or only one, steroid-sensitive rejection crisis) was significantly correlated with (1) a high pre-TLI helper/suppressor lymphocyte ratio, (2) a short interval between TLI and the time of transplantation, and (3) the occurrence of functional suppressor cells early after TLI. The most striking immunological changes provoked by TLI consisted of a long-term depression of the mixed lymphocyte reaction and of the phytohemagglutinin, and Concanavalin A or pokeweed-mitogen-induced blastogenesis. A rapid and complete recovery of the natural killer cell activity was observed after TLI. A permanent inversion of the OKT4+ (T helper/inducer) over OKT8+ (T suppressor/cytotoxic) lymphocyte ratio was provoked by a decrease of the OTK4+ subpopulation, together with a supranormal recovery of the OKT8+ lymphocytes. A majority of the latter lymphocytes did also express the Leu 7 and the Leu 15 phenotype.

Primary Sclerosing Cholangitis Associated with Membranous Nephropathy

Excerpt We report the case of a patient with primary sclerosing cholangitis associated with membranous nephropathy. A 41-year-old man had edema and fatigue. Serum albumin was 9.9 g/L (normal, 36 to...

Listeria monocytogenes meningitis.

The history and findings of all patients with Listeria meningitis admitted to the University Hospital of Leuven from 1967 to 1987 were reviewed. Listeriosis during pregnancy or the perinatal natal period was not considered. Predisposing conditions in these 23 patients included renal transplants (9), immunosuppressive therapy (2), diseases of the lympthoreticular system (3) and chronic alcoholism (1). One man had an inversed T4/T8 ratio. In 7 patients no underlying disorder was detected. Disease onset may be acute or subacute. There are no clinical features distinguishing Listeria meningitis from other acute bacterial meningitides. The number of leukocytes in the CSF varied from 3 to 3700, most often with a predominance of mononuclear cells. A decrease of the glucose level in the CSF was not always present. The initial gram stain was often unrevealing and it took up to 4 days for CSF cultures to become positive. Blood cultures were often important for the identification of the organism.