Reversible cardiac valvular disease in catastrophic antiphospholipid syndrome.

Catastrophic antiphospholipid syndrome (CAPS) is a severe form of antiphospholipid syndrome (APS). It frequently leads to multiorgan failure with an approximate mortality rate of 50%. The heart is involved in about 50% of the patients with CAPS. We report two cases with CAPS and severe heart manifestations, documented by echocardiography. Both women show regression of the valvular regurgitation under treatment. Valve replacement therapy was no longer necessary. In earlier studies and case reports, cardiac valve involvement had been characterised by valve thickening and vegetations. We suppose that (sometimes reversible) microvascular disturbances lead to valvular regurgitation via papillary muscle dysfunction and myocardial stunning.

An aid to the diagnosis of genetic disorders underlying adult-onset renal failure: a literature review.

Several genetic disorders can present in adult patients with renal insufficiency. Genetic renal disease other than ADPKD accounts for ESRD in 3% of the adult Dutch population. Because of this low prevalence and their clinical heterogeneity most adult nephrologists are less familiar with these disorders. As a guideline to differential diagnosis, we provide an overview of the clinical manifestations and the pathogenesis of the main genetic disorders with chronic renal insufficiency surfacing in adulthood and add an algorithm plus 4 tables. We also indicate where molecular genetics nowadays can be of aid in the diagnostic process. The following disorders are discussed by mode of inheritance: 1) Autosomal dominant: autosomal dominant polycystic kidney disease, nephropathies associated with uromodulin (medullary cystic disease and familial juvenile hyperuricemic nephropathy), renal cysts and diabetes syndrome, nail-patella syndrome, glomerulopathy with fibronectin deposits. 2) Not autosomal dominant: Nephronophthisis, Fabry disease, primary oxalosis, Adenine Phosphoribosyl Transferase deficiency, Alport syndrome, Lecithin-cholesterol acyltransferase deficiency, adult-onset cystinosis.

Citrate compared to low molecular weight heparin anticoagulation in chronic hemodialysis patients.

Citrate and nadroparin calcium, a low molecular weight heparin (LMWH), were compared in a randomized cross-over trial in 21 chronic hemodialysis patients regarding anticoagulation, calcium and magnesium kinetics, biocompatibility, dialysis efficiency, and aluminum contamination. Citrate was infused into the arterial line at a minimum rate of 0.68 mmol/min, combined with a calcium and magnesium-free dialysate and intravenous supplementation of calcium and magnesium at rates of 0.22 and 0.10 mmol/min, respectively. Seven patients with a dialysis session of six hours, received 2/3 of the nadroparin dose predialysis, and 1/3 after 2.5 hours (divided dose (DD) group). A single predialysis bolus injection of nadroparin was administered to eight patients not on coumarins [single dose (SD) group] and to six patients on coumarins [single dose + coumarins (SD + C) group], all with a dialysis session of four hours. Nineteen patients received a nadroparin dose of 200 ICU/kg. Two patients with a single dose, one of them on coumarins, received a dose of 150 ICU/kg because of a hematocrit < 0.30. With citrate systemic whole blood activated clotting time (ACT) remained unchanged, indicating efficient regional anticoagulation. After two hours of dialysis with nadroparin, systemic ACT increments, that is, the increase compared to predialysis, of the DD, SD, and SD + C groups were 8.8 +/- 1.5, 18.7 +/- 4.7, and 33.3 +/- 6.1 seconds, respectively (mean +/- SEM). Postdialysis ACT increments in these groups were 1.5 +/- 3.4, 17.7 +/- 6.8, and 30.3 +/- 8.0 seconds. Two hour increments of systemic activated partial thromboplastin time (APTT) of the DD, SD, and SD + C groups during nadroparin were 5.0 +/- 1.2, 15.1 +/- 2.7, and 32.2 +/- 5.5 seconds, respectively, and the corresponding postdialysis APTT increments were 2.9 +/- 1.4, 7.8 +/- 2.4, and 15.8 +/- 2.6 seconds. Two-hour anti-Xa increments of the DD, SD, and SD + C groups amounted to 0.34 +/- 0.07, 0.67 +/- 0.07, and 0.80 +/- 0.08 IU/ml. The respective postdialysis anti-Xa increments were 0.21 +/- 0.06, 0.58 +/- 0.06, and 0.71 +/- 0.08 IU/ml (All ACT, APTT and anti-Xa increments were significant; P < 0.05), except for the ACT increments and the postdialysis APTT increment of the DD group). These increments, together with unchanged prothrombin fragments 1 and 2 (PTF1 + 2), indicate systemic anticoagulation with nadroparin. The increments of serum calcium and magnesium during citrate were comparable to the increments observed with a dialysate containing 1.5 mmol/liter calcium and 0.75 mmol/liter magnesium used in combination with nadroparin. Ionized calcium increments during citrate were significant after the end of dialysis, while the dialysate containing 1.5 mmol/liter calcium induced significant increments during and postdialysis. No differences were observed between citrate and nadroparin regarding biocompatibility), (expressed as dialysis-induced leukopenia and thrombocytopenia), and dialysis efficiency [measured as dialyzer urea and creatinine clearance, normalized weekly whole body urea clearance (Kt/Vurea) and time averaged urea concentration (TACurea)]. The citrate solution, if sterilized in glass bottles, contained 2 to 3 micrograms aluminum per mmol citrate, the nadroparin solution 0.009 microgram per 1,000 ICU. Aluminum contamination of the citrate solution was prevented by sterilizing the solution in polypropylene bottles. In conclusion, citrate anticoagulation is regional and is indicated for hemodialysis patients with an active or recently active bleeding focus. However, the citrate solution should be sterilized in polypropylene containers to prevent aluminum contamination. LMWHs induce systemic anticoagulation during hemodialysis, and this effect is enhanced by concomitant coumarin use and mitigated by a divided LMWH dose regimen. For hemodialysis patients not at risk of bleeding, LMWHs provide a simple anticoagulation regimen.

[Current developments in the diagnosis and therapy of cytomegalovirus infections]. / Nieuwe ontwikkelingen in diagnostiek en therapie van cytomegalovirusinfectie.

We describe the case history of a 40-year-old, negroid woman with systemic lupus erythematosus who acquired a severe cytomegalovirus infection on immunosuppression; this infection was successfully treated with ganciclovir. New ideas in the management of CMV infections in immuno-compromised hosts are discussed. The traditional diagnostics are unsatisfactory, antibody detection being very insensitive and culture techniques too slow. A new diagnostic approach by detection of the immediate early antigens of the cytomegalovirus (CMV-IEA) using monoclonal antibodies is fast and reliable (sensitivity 93%, specificity 92%), even in case of immuno-deficiency. Finally we discuss the efficacy of the antiviral agent ganciclovir in the management of severe CMV infections.

IgA nephropathy is not induced in mice by oral administration of TNP-conjugated ovalbumin.

An IgA nephropathy model based on long-term oral administration of protein antigens was evaluated in three mouse strains using trinitrophenyl (TNP)-conjugated ovalbumin. Administration of the antigen for 14 weeks did not induce a significant IgA response nor deposition of IgA in the mesangium in any of the mouse strains. If, however, serum IgA anti-TNP antibodies were induced by intraperitoneal injection of anti-TNP producing MOPC-315 tumor cells, subsequent intravenous injection of antigen resulted in the deposition of IgA immune complexes in the mouse kidneys. Hematuria did not occur. In conclusion, previous data showing that long-term oral administration of protein antigens induces mesangial IgA deposits could not be confirmed with TNP ovalbumin. However, mesangial IgA deposits were obtained in animals treated with MOPC-315 tumor cells as described by Rifai et al. [J. exp. Med. 150: 1161-1173, 1979].

Toward individual prognosis of IgA nephropathy.

The individual prognosis of adult IgA nephropathy patients was studied using the proportional hazards model for the time from biopsy until endstage renal disease. After selection of the most relevant prognostic factors, the 75 patients were stratified with respect to hypertension and its treatment. In these strata, individual prognosis was based on the initial age-adjusted glomerular filtration rate, the initial proteinuria, the presence/absence of gross hematuria, and the presence/absence of microscopic hematuria. Using the scores of a patient on these variables, the probability of surviving any given period of time can be estimated either graphically or by calculation. Prediction is feasible up to about 10 years. Attention has been given to supply all relevant estimates with confidence limits. For each patient the estimated 5-year survival probability as predicted by the model was compared with the actual outcome.

Determination of inorganic sulphate in plasma by reversed-phase chromatography using ultraviolet detection and its application to plasma samples of patients receiving different types of haemodialysis.

The determination of sulphate in plasma is described, making use of reversed-phase high-performance liquid chromatography with ultraviolet detection. The concentration of inorganic sulphate determined in plasma of twenty healthy volunteers was 0.307 +/- 0.092 mmol/l (mean +/- S.D.). In one stable chronic dialysis patient the kinetics of plasma sulphate removal were monitored during and after one single pass dialysis. In addition, plasma sulphate concentrations were determined in three stable chronic dialysis patients during a consecutive scheme of two single pass dialyses, five Redy dialyses and three single pass dialyses. As expected, plasma sulphate accumulates in plasma to a high steady-state level under Redy dialysis, whereas during single pass dialysis sulphate is efficiently removed.

Subentities within adult primary IgA-nephropathy.

Since its definition is purely descriptive, IgA-nephropathy (IGAN) may comprise more disease entities which share the (epi)phenomenon of mesangial IgA-depositions. IGAN patients with macroscopical hematuria (macro-H) differ from the other IGAN patients in 9 aspects: history, HLA-DR, Gm-allotypes, actuarial kidney survival, initial creatinine clearance, initial proteinuria, initial microhematuria, age at presentation and light microscopy of the renal biopsy. The difference in the last five parameters may either be explained by the existence of subentities or by earlier detection of patients with macro-H. The dissimilarity in the first four parameters can only be due to the former theory. Therefore, we conclude that IGAN probably comprises at least two disease entities.

Reversible diminished renal 99mTc-DMSA uptake during converting-enzyme inhibition in a patient with renal artery stenosis.

A patient is described who had accelerated hypertension and unilateral renal artery stenosis, and who developed further deterioration in renal function during treatment with captopril, an angiotension-I (AI) converting-enzyme inhibitor. 99mTc-DMSA uptake was greatly diminished in the stenotic kidney, although renal blood flow and handling of 131I-hippurate was preserved. Uptake of 99mTc-DMSA in the affected kidney returned after substitution of captopril by the vasodilator minoxidil, while a comparable degree of blood pressure control was maintained. Thus, caution must be taken when interpreting results of 99mTc-DMSA scintigraphy in patients with proven or suspected renal artery stenosis treated with an AI converting-enzyme inhibiting drug. Moreover, our finding points to the importance of glomerular filtration in the renal handling of 99mTc-DMSA.

Immunogenetic differences in subpopulations of patients with IgA nephropathy (Berger's disease).

Gm and Km as well as HLA-A, HLA-B, and HLA-DR phenotype frequencies were examined in 64 well-defined IgA nephropathy patients. The patients were divided into subpopulations according to clinical symptoms, e.g. macrohematuria and chronic renal failure (CRF). In patients with CRF the frequency of the Gm1,3,17;5,13,21 phenotype tended to be increased (p = 0.016; pcorr = 0.08). The frequency of the HLA-DR phenotype with only one antigen (HLA-DR-) was increased in the whole population (p less than 0.001; pcorr less than 0.011), which appeared to be confined to the patients with macrohematuria (p less than 0.001; pcorr less than 0.01) and non-CRF (p less than 0.001; pcorr less than 0.011). Patients with the Gm1,3,17;5,13,21 phenotype developed a CRF significantly earlier (p = 0.009; pcorr = 0.045) than patients with other Gm phenotypes. These data suggest that clinically observed subpopulations of IgA nephropathy patients differ in immunogenetic background.

Intravenous digital subtraction angiography of arteriovenous fistulas and shunts for hemodialysis.

Surgical reconstruction of vascular access in hemodialysis patients requires solid information on the site and type of the shunt failure. In 21 cases (16 patients) analysis of angioaccess failure included digital subtraction angiography. With this technique, information on anatomy and rheological pattern enabled us to plan specific surgical procedures during which preoperative diagnoses were confirmed.

Vascular permeability increasing factor (VPF) in IgA nephropathy.

Peripheral blood mononuclear cells (PBC) from non-nephrotic and nephrotic patients with different glomerulopathies were tested for their potential to produce vascular permeability increasing factor (VPF) after stimulation with Concanavalin-A (Con-A) in vitro. Supernatants from cultures of PBC from patients with IgA nephropathy were injected intradermally into the skins of normal Wistar rats which were given Evans blue dye solution intravenously. The mean extravasation of dye after 60 minutes was taken as a standard for the induction of local vascular permeability. Using a routine vascular permeability assay based on this principle similar studies were done with supernatants from cultures of PBC from nephrotic subjects with minimal change disease (MCD), or membranous nephropathy (MGN) and from healthy donors. The results show that cultures of PBC from non-nephrotic subjects with IgA nephropathy as well as from nephrotic MCD patients produced VPF in their supernatants whereas lymphocytes from nephrotic MGN subjects or normal donors did not. It is concluded that the production of VPF in stimulated PBC cultures from patients with IgA nephropathy or MCD might reflect altered T-cell function in these diseases, and that there is no direct relationship between VPF production and increased glomerular permeability.