Unsuccessful transjugular intrahepatic portosystemic shunt for a patient with right heart failure and portal hypertension.

A 60-year-old women with a history of congenital pulmonary valve stenosis developed right heart failure, cardiac cirrhosis and end-stage renal disease requiring renal replacement therapy. Cirrhosis was complicated by portal hypertension, resulting in intractable gastro-intestinal bleedings despite optimal treatment with beta-blockers and endoscopic band ligation. Because of fears for worsening right heart failure, a decision for placement of a transjugular intrahepatic portosystemic shunt (TIPS) was initially turned down. However, as intractable bleeding problems persisted and caused heavy transfusion needs, TIPS was ultimately performed as a rescue procedure. Although TIPS successfully reduced the hepatic venous pressure gradient from 16 mmHg to 4 mmHg, portal pressure remained high at 14 mmHg because of persisting right heart failure with elevated central venous pressure. Hepatic encephalopathy soon developed after TIPS placement and culminated in multi-organ failure after another episode of gastro-intestinal bleeding. At this point, the family of the patient decided to withdraw care and the patient died subsequently. This case illustrates how important it is to diagnose and optimally treat right heart failure before cardiac cirrhosis with its impending complications emerges. Although TIPS may effectively treat complications of portal hypertension in the context of cirrhosis, persisting right heart failure may abrogate its beneficial effects.

Hypophosphatemic osteomalacia: an unusual clinical presentation of multiple myeloma.

An unusual case of a 75-year-old man is presented who had multiple stress fractures due to adult onset hypophosphatemic osteomalacia, which was the result of Fanconi syndrome, with light chain cast proximal tubulopathy due to multiple myeloma. A 75-year-old man presented with diffuse pain and muscle weakness. He had multiple stress fractures, low serum phosphate, decreased renal tubular reabsorption of phosphate, and normal PTH and FGF23, indicating adult onset hypophosphatemic osteomalacia. Phosphate supplements with calcitriol resulted in clinical recovery and healing of stress fractures. Because of proteinuria, a renal biopsy was performed that revealed Fanconi syndrome with light chain cast proximal tubulopathy and light kappa chains were found in serum and urine. A bone biopsy confirmed the diagnosis of multiple myeloma, and treatment with chemotherapy resulted in cytological and clinical recovery.

Maternal venous Doppler characteristics are abnormal in pre-eclampsia but not in gestational hypertension.

OBJECTIVE: To compare functional characteristics of maternal thoraco-abdominal arteries and veins in proteinuric and non-proteinuric hypertension in pregnancy. METHODS: This retrospective study included women with singleton pregnancies during the third trimester, which were either uncomplicated or complicated with different clinical types of hypertension: non-proteinuric gestational hypertension (GH), early-onset pre-eclampsia (PE) diagnosed < 34 weeks or late-onset PE diagnosed ≥ 34 weeks. Demographic maternal and neonatal data were recorded, together with maternal serum and urine analytes. All women underwent standardized automated blood-pressure measurement, together with non-invasive impedance cardiography (ICG), for measurement of cardiac output (CO), aortic flow velocity index (VI) and aortic flow acceleration index (ACI). A standardized combined Doppler-electrocardiography assessment of maternal venous hemodynamics was performed to measure renal interlobar vein impedance index (RIVI), hepatic vein impedance index (HVI) and venous pulse transit time (VPTT) in liver and kidneys. Finally, resistance index (RI), pulsatility index (PI) and arterial pulse transit time (APTT) were measured in the uterine arcuate arteries. Mann-Whitney U-tests and Fisher's exact tests were used for intergroup comparisons, and linear dependence between variables was assessed using Pearson's correlation coefficient (r). RESULTS: A total of 150 pregnancies were evaluated: 22 with uncomplicated pregnancy, 41 GH, 31 early PE and 56 late PE. Aortic VI and ACI were lower in GH, early PE and late PE than in uncomplicated pregnancy. Both early PE and late PE differed from GH by having shorter APTT in the uterine arcuate arteries and higher RIVI. Hemodynamic abnormalities were most pronounced in early PE, during which uterine arcuate artery RI was higher and VPTT in kidneys was shorter than in late PE. There was a significant correlation between degree of proteinuria and RIVI for the left (r = 0.381) and right (r = 0.347) kidney in late PE, but this was not true for early PE. CONCLUSIONS: There is a gradient of worsening arterial and venous hemodynamic abnormalities from GH to late PE and then to early PE. Venous hemodynamic abnormalities are present only in PE, with a linear correlation between proteinuria and RIVI in late PE. The role of the maternal venous compartment in the pathophysiology and etiology of PE-related symptoms may be much more important than considered at present.

Kinin generation by hemodialysis membranes as a possible cause of anaphylactoid reactions.

1. Severe anaphylactoid reactions have been reported in some patients treated with angiotensin converting enzyme (ACE) inhibitors during hemodialysis with a polyacrylonitrile (PAN) membrane. Generation of bradykinin via contact activation at the negatively charged membrane surface and reduced bradykinin breakdown due to ACE inhibition have been suggested as possible causes. This hypothesis was evaluated in the present study. 2. PAN or cellulose dialyzer membranes were incubated with plasma at different concentrations of ACE inhibitor. The rate and extent of kinin accumulation was dependent on the ACE inhibitor concentration. 3. Bradykinin levels were determined in "historical" plasma samples drawn from patients treated with ACE inhibitor at the onset of anaphylactoid reactions during hemodialysis with PAN dialyzers. The kinin levels were significantly higher (2.4 +/- 0.05 pmol/ml) than in samples from a group of control patients (0.29 +/- 0.02 pmol/ml). 4. Plasma kinin levels were measured in patients who developed anaphylactoid reactions during dialysis with a PAN membrane though not being treated with ACE inhibitor. At the onset of the reaction, kinin levels increased to 2.1 pmol/ml in the line entering the dialyzer and to 10.5 pmol/ml in the line leaving the dialyzer compared to not more than 0.12 pmol/ml upon dialysis with other membranes. 5. These in vitro and in vivo results demonstrate that contact of blood with a polyacrylonitrile membrane leads to the generation of kinins which accumulate if ACE is inhibited. It is very likely that kinin accumulation in the circulation is the cause of anaphylactoid reactions during hemodialysis with PAN membranes in patients treated with ACE inhibitors and, in some cases, in patients not receiving ACE inhibitor medication.

Bradykinin is a mediator of anaphylactoid reactions during hemodialysis with AN69 membranes.

Anaphylactoid reactions (AR) are the most feared complications of hemodialysis. Recently, a high incidence of AR has been reported during dialysis with AN69 membranes in patients treated with ACE inhibitors. Plasma levels of C3a, histamine and bradykinin were measured in 12 patients at the onset of AR during dialysis with AN69. We also investigated bradykinin generation in 10 symptom-free patients dialyzed with four different membranes. None of the 12 patients studied during AR displayed excessive complement activation or histamine release. In contrast, high bradykinin plasma levels (2392 +/- 53 fmol/ml; mean +/- SEM) were observed in all nine patients of whom bradykinin was measured. One patient developed two consecutive episodes of hypersensitivity on AN69 membranes even without taking ACE inhibitors. Bradykinin levels were high in both episodes (5280 and 10467.7 fmol/ml). Furthermore, this patient showed no symptoms and normal bradykinin levels (123.4 fmol/ml) when dialyzed with other membranes. The role of the membrane type in the AR is further substantiated by the observation that AN69 also provoked a significantly higher bradykinin generation (327.6 +/- 18 fmol/ml; mean +/- SEM) during symptom-free sessions compared to other membranes like CuprophanR (5.1 +/- 7.3), HemophanR (17.2 +/- 6.3) and PolysulfoneR (39.7 +/- 6.6). Our findings strongly suggest that bradykinin is the principal mediator of AR during hemodialysis with AN69 membranes. To our knowledge it is the first time that data support the hypothesis of a more general role of bradykinin in shock-like symptoms. Furthermore, bradykinin generation must be regarded as a new marker of biocompatibility of extracorporeal treatments.

The measurement of fecal thyroxine in the diagnosis of thyrotoxicosis factitia.

Two patients with prolonged thyrotoxicosis are presented with low radioiodide uptake, low-normal serum thyroglobulin concentrations, and low iodide content of the neck on x-ray fluorescence studies. The surreptitious intake of thyroid hormone was directly proven by a high fecal concentration of T4 (12.38 and 23.99 nmol/g) compared with low concentrations in healthy subjects (1.03 +/- 0.64 nmol/g; mean +/- SD, n = 6) and in patients with hyperthyroidism due to Graves' disease (1.93 +/- 1.86; n = 8). Fecal thyroid hormone measurement may help to provide formal proof of factitious thyrotoxicosis.

Surrogate markers are not useful for identification of HCV carriers in chronic hemodialysis patients.

Several diagnostic hepatitis C assays have been developed for the detection of antibodies to different antigens of the virus. This virus is the major cause of non-A, non-B hepatitis. Seventy-nine patients undergoing chronic hemodialysis and/or hemofiltration were tested for the presence of anti-HCV antibodies (anti-C-100-3 antibodies and anti-core antibodies), anti-hepatitis B core antibodies (anti-HBc), and aminotransferases (ALT). Seven patients were positive by one or more of the anti-HCV enzyme linked immunoassays (EIAs), while HCV-RNA was detectable in only four patients. These four patients had at least one, but not necessarily the same, positive anti-HCV EIA. HCV-RNA was not detected in patients who had no antibodies as determined by all six anti-HCV EIAs. All patients with a marker for HCV infection had persistent normal levels of transaminases. Three patients had elevated ALT values without a marker for HCV infection and suffered from hepatitis B virus infection. Anti-HBc was detected in 27/72 patients without any marker and in four patients with a marker of HCV infection. However, HCV-RNA was detectable in only one of these four anti-HBc positive patients. It is concluded that surrogate markers (anti-HBc and serum transaminases) are not useful for identification of HCV carriers in chronic hemodialysis patients.

Angiotensin-converting-enzyme inhibitors and anaphylactoid reactions to high-flux membrane dialysis.

In a retrospective study, 9 of 236 haemodialysis patients treated with high-flux polyacrylonitrile 'AN 69' membranes were found to have had anaphylactoid reactions. Treatment with angiotensin-converting-enzyme (ACE) inhibitors had been recently started in all 9 affected patients; only 5 of 227 unaffected patients had been treated with ACE inhibitors, and anaphylactoid reactions disappeared after discontinuation of ACE inhibitors.

Fatty liver hepatitis and type 5 hyperlipoproteinemia in juvenile diabetes mellitus. Case report and review of the literature.

A 28-year-old man with poorly controlled juvenile-onset diabetes mellitus presented with jaundice and type 5 hyperlipoproteinemia. A liver biopsy showed fatty liver hepatitis (steatonecrosis). This case represents one end in a spectrum of lipid disorders and liver disease in diabetes mellitus. With increasing insulin deficiency, liver steatosis and the more common type 4 hyperlipoproteinemia pattern may progress to fatty liver hepatitis and type 5 hyperlipoproteinemia.

Growing bone cysts in long-term hemodialysis.

All patients with chronic renal failure undergoing hemodialysis for more than 10 years in the university hospitals of Leuven were selected for this study. The medical records and radiographs of these 21 patients were studied retrospectively. Skeletal surveys were examined for the presence and location of subchondral cysts. The predialysis films and the films taken after 5, 10, 15 and 20 years of dialysis were reviewed. Subchondral cysts that grew in size and number were found in the wrist, humeral head, hip, and patella. Accurate measurements were made of cysts in the wrist and compared with a control group. In the dialysis group, cystic involvement of the wrist was more common and the size and number of the cysts were larger. Soft tissue swelling was seen in the dialysis group but not in controls. Soft tissue swelling was assessed on shoulder radiographs by measuring the acromiohumeral distance (ACD) and in the knees by ultrasonic measurement of synovial thickness. In 11 patients synovial or bone biopsies or aspirated synovial fluid were available. All these patients had swollen joints and multiple subchondral periarticular cysts. Amyloid deposition was found in ten of these patients, and this proved to be composed of B2 microglobulins in seven.

Haemostatic effects of recombinant human erythropoietin in chronic haemodialysis patients.

Recombinant human erythropoietin was administered for up to 40 weeks to nine patients on chronic haemodialysis. From the third week of administration onwards, not only haemoglobin and haematocrit but also the platelet count rose, the latter, however, transiently. Subnormal platelet aggregation before therapy also improved transiently and in parallel with the erythropoietin dosage. The bleeding time normalized in almost all patients. There were no major side-effects. We conclude that recombinant erythropoietin improves haemostasis in chronic haemodialysis patients by increasing the haematocrit and in addition transiently enhances platelet number and function.