Bo G. Danielson

Biochemical and Clinical Effects of the Prophylactic Treatment of Renal Calcium Stones with Magnesium Hydroxide

Prophylactic treatment with magnesium hydroxide ws instituted in 56 consecutive cases with renal calcium stones. The patients had been investigated previously with regard to the magnesium metabolism. The urinary magnesium excretion increased promptly and remained on a higher level during treatment. No changes were observed in the serum or urinary calcium concentrations. Most patients have undergone treatment for at least 2 years and 45 have been free of recurrences of formations of new stones. The mean stone episode rate during treatment was 0.03 stones per year compared to 0.8 stones per year before treatment was instituted. The natural history of stone disease also was followed in 34 patients with stones who had received no prophylactic therapy and 15 have experienced recurrences after 2 years. Therefore, in comparison, treatment with magnesium hydroxide appeared to reduce the recurrence rate. Apart from minor gastrointestinal discomfort no adverse effects were observed during treatment.

Incidence and clinical importance of renal tubular defects in recurrent renal stone formers.

Renal tubular function was studied in 318 consecutive recurrent renal stone formers. Impaired acidification capacity was found in 19% of the patients, and tubular proteinuria in 13% of the patients. Most of the patients with defective acidification of the urine had the incomplete form of renal tubular acidosis (RTA), rpoximal and distal defects being equally common. The incidence of impaired acidification was much higher in the female (38%) than in the male (13%) stone formers. A further analysis of the clinical picture in patients with acidification defects revealed a more severe stone disease than among other stone formers. Characteristic findings were an early onset, multiple recurrences were an increased need for surgery. Stone analyses showed a high frequency of calcium phosphate stones. Investigations of renal tubular functions appear to be a valuable adjunct in the evaluation of recurrent renal stone disease.

Treatment of recurrent calcium stone formation with cellulose phosphate.

Sodium cellulose phosphate was given to 35 patients for recurrent formation of calcium-containing stones. During therapy urinary calcium decreased by 40% in the first month and remained at this lower level. In addition, urinary magnesium excretion was reduced and the urinary magnesium/calcium ratio remained unaffected. In these patients, who mostly had had calcium oxalate stones, the prophylactic effects of sodium cellulose phosphate was poor, with a 47% recurrence rate after 2 years. This lack of prevention, despite the significant reduction of the urinary calcium, is assumed to be owing to the effects of treatment on magnesium and oxalate metabolism. Side effects were common, mainly consisting of moderate gastrointestinal discomfort, and caused withdrawal of treatment in 8 patients. This fact contributes further to our opinion that sodium cellulose phosphate is not the drug of choice in cases of calcium oxalate stone formation.

Crystal inhibition: the effects of polyanions on calcium oxalate crystal growth

The inhibition of calcium oxalate crystal growth by the glycosaminoglycans, chondroitin sulphates and heparin, by the low-molecular-weight heparin analogue pentosan polysulphate and by Tamm-Horsfall glycoprotein extracted from human urine, was measured by using a seeded crystal procedure and compared with the inhibition by pyrophosphate. It was found that the most pronounced inhibition was obtained with the polyanions with the highest charge density, i.e., heparin and pentosan polysulphate. Tamm-Horsfall glycoprotein caused an inhibition of a similar magnitude as urinary chondroitin sulphates. Urinary polyanions with a high affinity to Sepharose 4B were more efficient inhibitors than those with a low or no affinity to the gel. It is concluded that urinary polyanions are important inhibitors of calcium oxalate crystal growth and that the potency of inhibition increases with the charge density.

Blood viscosity and peripheral vascular resistance in patients with untreated essential hypertension

Objectives: The viscosity of blood is increased in patients with essential hypertension. The aim of the present study was to investigate the importance of the different variables of blood rheology to total peripheral resistance, and to elucidate whether inappropriate regulation of the formation of erythropoietin could be important. Design: Nineteen consecutive patients with untreated essential hypertension were examined and compared with a group of matched healthy volunteers. Methods: The haemorheologic variables were assessed by rotational viscometry and the haemodynamic variables by bioimpedance cardiography. The serum concentrations of erythropoietin were determined by radioimmunoassay. Results: The whole blood viscosity and peripheral resistance index were elevated in the hypertensive group. The two variables were positively correlated with each other (r=0.68, P=0.0015). The plasma viscosity and erythrocyte aggregation tendency were increased and the erythrocyte deformability, measured as fluidity, was decreased in the hypertensive patients. In the male subpopulation (n=12) the aggregation tendency was positively, and the deformability negatively, correlated with body mass index. The serum concentrations of erythropoietin were equal in the two groups. Conclusions: The increased total peripheral resistance in patients with essential hypertension may in part be explained by an increased blood viscosity, but the possibility of an opposite cause-effect relationship must also be taken into consideration. The haemorheological abnormalities observed in the present patients cannot be explained by high serum levels of erythropoietin.

Endotoxemia in Chronic Renal Failure

In the past years dialyzers have been improved, and consequently pyrogenic reactions have become rare. However, some patients in our dialysis unit have shown symptoms during hemodialysis which we suspected could be caused by endotoxins. These patients, as well as controls without similar symptoms, had elevated levels of circulating endotoxin. We therefore measured endotoxin in blood from patients with chronic renal failure and different kinds of treatment. Serum samples were analyzed with a sensitive method described in the literature, using a chromogenic substrate and Limulus amebocyte lysate. In patients on hemodialysis (mean +/- SEM) the endotoxin value in samples taken immediately before dialysis was 40 +/- 4.7 ng/l and significantly elevated (p less than 0.001) compared with the endotoxin value (7 +/- 0.6 ng/l) found in the healthy reference group. Increased endotoxin levels were also seen in patients on hemofiltration (19 +/- 7.5 ng/l) and in patients with conservative treatment and various degrees of renal insufficiency (17 +/- 2.5 ng/l). Patients on peritoneal dialysis and renal-transplanted patients had levels not different from the controls. The mechanism behind endotoxemia in uremia is unknown but may partly be explained by reduced endotoxin elimination due to impaired liver macrophage function. The differences in endotoxin levels in patients on peritoneal or hemodialysis treatment may reflect that extracorporeal circulation enhances endotoxin entrance to the circulation and/or that endotoxin clearance is dependent on the dialysis regimen.

Intestinal oxalate and calcium absorption in recurrent renal stone formers and healthy subjects.

The fractional intestinal absorption of oxalate and calcium was investigated by isotope techniques in 20 normal subjects and in 12 idiopathic calcium oxalate stone formers. The greatest amount of 14C-oxalate was excreted during the first six hour period in controls as well as in stone formers. The stone formers had a greater intestinal uptake of oxalate (11 +/- 5.1%) than the controls (6.2 +/- 3.7%; p less than 0.01). There was no significant relationship between the fractional absorption of oxalate and the total urinary oxalate excretion. The stone formers also had a higher fractional uptake of calcium compared to the controls (55 +/- 11% vs. 47 +/- 9.1%; p less than 0.05). There was a positive relationship (r = 0.47) between the urinary excretions of calcium and oxalate in the stone formers. During these conditions no correlation could be demonstrated between the fractional absorptions of oxalate and calcium, neither in the stone formers nor in the controls. In conclusion, patients with recurrent formation of calcium oxalate containing stones appear to have an enhanced intestinal uptake of both oxalate and calcium. This disturbance could be of primary pathogenic importance for their stone forming propensity.

The Relation Between Urinary Tract Infections and Stone Composition in Renal Stone Formers

During a seven-year period (1975-1981) a total of 1325 patients hospitalized for stone disease were studied as to the occurrence of positive urine cultures. Urinary stones from 535 surgically treated patients were analyzed with infrared spectrophotometry and the relationships between stone composition, level of surgery and bacteriological strains were studied. Positive urinary cultures were found in 34% of the surgically treated patients and in 21% of those not operated upon. Among the surgically treated patients with urinary tract infection (UTI) E. coli was the most frequent microorganism (35%), followed by Proteus (28%). Patients with Proteus infection had the highest frequency of UTI episodes, most of which occurred before hospitalization. There was a higher frequency of magnesium ammonium phosphate (MAP) calculi among patients with Proteus infection than among those with non-Proteus infection, in whom no difference in stone composition was found. Patients infected with E. coli had more phosphate-containing stones (CaP+MAP) than non-infected patients. The highest frequency of oxalate calculi (CaOx+CaOx/CaP) was found among patients without infection. No E. coli infections were seen in male patients with CaP and MAP calculi. MAP stones were most often found in the kidney and oxalate stones in the ureter.

Neutrophil and eosinophil degranulation during hemodialysis are mediated by the dialysis membrane.

During hemodialysis of heparinized blood without having a patient in the circuit, the serum concentrations of lactoferrin, myeloperoxidase (MPO) and eosinophil cationic protein (ECP) steadily increased, indicating neutrophil and eosinophil degranulation. The increments in serum of these granular proteins were more pronounced using plate dialyzers than capillary dialyzers. The release of granule constituents does not seem to reflect merely a sequestration of granulocytes in the dialyzer, since the increase of the serum concentrations of lactic dehydrogenase was very modest. The intracellular contents of lactoferrin, MPO, lysozyme and ECP were reduced after experimental dialysis in the granulocytes isolated from the blood, indicating that the cells in association with degranulation were not entrapped in the dialyzer. The relatively modest increase of the plasma concentrations of lysozyme during experimental hemodialysis, in spite of the reduction of the intracellular content of lysozyme, was explained by the propensity of lysozyme for adhering to the dialysis membrane. Serum samples obtained at different times during dialysis did not induce an enhanced release of granular proteins from isolated granulocytes in vitro. The earlier observed increase during hemodialysis of the serum concentrations of granular proteins in uremic patients can be explained by the dialysis membrane triggering granulocytes to degranulate.

Renal anaemia treatment with recombinant human erythropoietin increases cardiac output in patients with ischaemic heart disease.

An increase in blood pressure is common during treatment of renal anaemia with recombinant human erythropoietin (rhEPO). Concomitant findings of a decrease in cardiac output indicate that an increase in the peripheral flow resistance underlies the increase in blood pressure. The aim of this study was to elucidate the haemodynamic changes during rhEPO treatment in patients with ischaemic heart disease (IHD). Haemodynamic variables were assessed by impedance cardiography in 18 consecutive patients with renal anaemia before and after rhEPO treatment. IHD was found in eleven of these patients. The remaining seven served as controls. Before rhEPO treatment, the cardiac index was decreased in the group of patients with IHD, compared with controls and healthy subjects. Due to an increase in stroke index, the cardiac index increased during rhEPO treatment and reached values equal to those in the control group. The blood pressure increased and the increase in mean arterial pressure was correlated to the increase in cardiac index. Apparently the patients with IHD were unable to compensate for anaemia by increasing their cardiac index. Anaemia treatment increased cardiac index, which in turn caused an increase in blood pressure in these patients.