Transperitoneal transport in diabetic and non-diabetic patients on peritoneal dialysis.

To investigate differences in the transport characteristics of the peritoneal membrane between diabetic and non-diabetic patients on chronic peritoneal dialysis, a study was conducted in 21 non-diabetic and 18 diabetic patients. Transperitoneal transport of small solutes was evaluated in terms of the mass transfer area coefficients (urea, creatinine and glucose), ultra-filtration sieving coefficients (urea and creatinine) and by peritoneal equilibration test results. The capacity of the peritoneal membrane to transport macromolecules was evaluated by albumin mass transfer rates and clearances of albumin. Transperitoneal water transport was evaluated by the ultra-filtration properties and the lymphatic flow rates. Finally, the whole-body capillary permeability was estimated by measuring the unidirectional flux of albumin across the capillary wall, i.e. the transcapillary escape rate of 125I-labelled human albumin. Despite a significantly increased transcapillary escape rate of albumin in the diabetic patients, no differences in peritoneal membrane characteristics could be demonstrated between diabetic and non-diabetic patients on peritoneal dialysis.

A prospective study of transperitoneal transport in patients undergoing peritoneal dialysis.

A prospective one-year follow-up study of the functional characteristics of the peritoneal membrane was conducted in 20 peritoneal dialysis patients. Ten patients had at least one episode of peritonitis during the follow-up period. Changes in the transperitoneal transport of small solutes were evaluated by the mass transfer area coefficients (urea, creatinine, and glucose), ultrafiltration sieving coefficients (urea and creatinine), and peritoneal equilibration test results. Changes in the capacity of the peritoneal membrane to transport macromolecules were evaluated by means of albumin mass transfer rates. Finally, changes in transperitoneal water transport were evaluated by means of the ultrafiltration properties and the lymphatic flow rates. After one year of follow-up, transport of water and the investigated solutes had not changed significantly. Even episodes of peritonitis had no permanent influence on the transport function of the peritoneal membrane. The intraperitoneal residual volumes before instillation were significantly larger in patients who developed peritonitis during the follow-up period compared to patients who did not. Over a one-year period, no changes in peritoneal membrane characteristics could be demonstrated. A large residual volume of dialysate may be a marker of increased risk of getting peritonitis.

The transport of phosphate between the plasma and dialysate compartments in peritoneal dialysis is influenced by an electric potential difference.

Six kinetic models of transperitoneal phosphate transport were formulated and validated on the basis of experimental results obtained from 22 non-diabetic patients undergoing peritoneal dialysis. The models were designed to elucidate the presence or absence of diffusive, non-lymphatic convective, and lymphatic convective phosphate transport. Calculations allowed for a 20% protein binding of phosphate. The validation procedure demonstrated that only diffusive and non-lymphatic convective phosphate transport mechanisms were identifiable. A lymphatic convective phosphate transport mechanism was not identifiable. Furthermore, it was demonstrated that the electrochemical gradient between plasma water and dialysate favours the diffusive phosphate transport, and both electric and chemical potentials must be taken into account in calculations of the transperitoneal phosphate transport.

Transperitoneal transport of sodium during hypertonic peritoneal dialysis.

The mechanisms of transperitoneal sodium transport during hypertonic peritoneal dialysis were evaluated by kinetic modelling. A total of six nested mathematical models were designed to elucidate the presence or absence of diffusive, non-lymphatic convective and lymphatic convective solute transport. Experimental results were obtained from 26 non-diabetic patients undergoing peritoneal dialysis. The model validation procedure demonstrated that only diffusive and non-lymphatic convective transport mechanisms were identifiable in the transperitoneal transport of sodium. Non-lymphatic convective sodium transport was the most important quantitative transport mechanism during the first 90 min of the dwell. Significant sodium sieving was demonstrated and explains the observation of hypernatremia in dialysis with hypertonic dialysis fluid.

An evaluation of twelve nested models of transperitoneal transport of urea: the one-compartment assumption is valid.

Models of transperitoneal urea transport are generally based on the one-compartment assumption, i.e. that the plasma water urea concentration in the peritoneal capillary bed is equal to the plasma water urea concentration in the peripheral veins. The aim of this study was to investigate the mechanism(s) of transperitoneal urea transport and to test the one-compartment assumption for urea. A total of 12 nested models were formulated and validated on the basis of experimental results obtained from 23 non-diabetic patients undergoing peritoneal dialysis. The validation procedure demonstrated that transperitoneal transport of urea probably involves diffusion, non-lymphatic convection and lymphatic convection. It was furthermore demonstrated that the inclusion of lymphatic convection changes the mass transfer area coefficient considerably. Finally, no deviation from the one-compartment assumption was demonstrated by our results.

Parameter estimation in six numerical models of transperitoneal transport of potassium in patients undergoing peritoneal dialysis.

The mechanisms of transperitoneal potassium transport during peritoneal dialysis were evaluated by validation of different mathematical models. The models were designed to elucidate the presence or absence of diffusive, non-lymphatic convective and lymphatic convective solute transport. Experimental results were obtained from 26 non-diabetic patients undergoing peritoneal dialysis. The validation procedure demonstrated that models including both diffusive and non-lymphatic convective solute transport were superior to the other models. Lymphatic convective solute transport was not identifiable. Furthermore, it was demonstrated experimentally that the equilibrium distribution of potassium between plasma water and dialysate did not differ from a Donnan equilibrium, although the precondition of the Donnan equilibrium was not fulfilled, i.e. the volumes on each side of the membrane were not constant and dialysate was not an ultrafiltrate of plasma.

Collagen markers in peritoneal dialysis patients.

Possible relationships between the dialysate-to-plasma creatinine equilibration ratio (D/Pcreatinine 4 hour), duration of peritoneal dialysis treatment, number of peritonitis episodes, and mass appearance rates of three connective tissue markers [carboxyterminal propeptide of type I procollagen (PICP), aminoterminal propeptide of type III procollagen (PIIINP), and carboxyterminal telopeptide of type I collagen (ICTP)] were studied in 19 nondiabetic peritoneal dialysis patients. The absence of correlation between the mass appearance rates of the markers and the duration of dialysis treatment as well as the number of peritonitis episodes supports the concept that peritoneal dialysis does not cause persistent changes in the deposition and degradation rates of collagen. A correlation between the D/Pcreatinine 4 hr and the PICP mass appearance rates was found. Since it is unlikely that transperitoneal transport alone is responsible for the appearance of PICP in dialysate, this might reflect an association between a large peritoneal surface area and the amount of submesothelial connective tissue.

Parameter estimation in six numeric models of transperitoneal transport of glucose.

Six competing kinetic models of transperitoneal glucose transport were formulated and validated. The models were designed to elucidate the presence or absence of diffusive, nonlymphatic convective and lymphatic convective solute transport. The validation procedure included an assessment of theoretical and practical identifiability, goodness of fit, residual error analysis, and plausibility of parameter estimates. Experimental results were obtained from 21 patients without diabetes. The validation procedure demonstrated that the model that only included diffusion was superior to the other models. Theoretically, both nonlymphatic convective and lymphatic convective transports might exist. However, neither the ultrafiltration sieving coefficient nor the lymphatic flow rate were practically identifiable, probably because any amount of glucose transported by nonlymphatic convective and lymphatic convective transport mechanisms was negligible compared with the amount transported by diffusion. Based on these results, there appear to be problems measuring convective solute transport parameters when the solute transport is in the dialysate-to-blood direction while the fluid transport is in the blood-to-dialysate direction.

Transperitoneal transport of creatinine. A comparison of kinetic models.

Six kinetic models of transperitoneal creatinine transport were formulated and validated on the basis of experimental results obtained from 23 non-diabetic patients undergoing peritoneal dialysis. The models were designed to elucidate the presence or absence of diffusive, non-lymphatic convective and lymphatic convective solute transport. The validation procedure included an assessment of theoretical (a priori) and practical (a posteriori) identifiability, goodness of fit, residual error analysis and plausibility of parameter estimates. The results of the validation procedure demonstrate that the model including all three forms of transport is superior to other models. We conclude that the best model of transperitoneal creatinine transport includes diffusion, non-lymphatic convective transport and lymphatic convective transport.

Van Beaumont's formula is valid during haemodialysis. Spectrophotometric determination of body circulating haemoglobin.

Van Beaumont's formula is a convenient method to calculate changes in plasma volume from changes in haematocrit. The calculation is based on the assumption of a constant body red-cell volume. In order to evaluate the validity of this assumption during isovolaemic haemodialysis, we measured body circulating haemoglobin, blood volume and plasma volume by carbon monoxide dilution. No change in body circulating haemoglobin or plasma volume occurred by either method. Therefore, we conclude that van Beaumont's formula is valid during isovolaemic haemodialysis.

[Systemic lupus erythematosus. 2. Factors of predictive significance for survival]. / Systemisk lupus erythematosus. 2. Faktorer med praediktiv betydning for overlevelsen.

Sixty-one of 173 patients with systemic lupus erythematosus followed for a mean of 13.9 years had severe infections which influenced their survival more than could be accounted for by the mortality (20 per cent) caused by the infections. Patients with infections had more SLE manifestations than patients without infections, and they died of lupus manifestations more often than patients without infections. Patients who went into a permanent remission and patients who died of lupus differed most markedly by the rates of infection. The rate of infection was increased more than tenfold in patients treated with high dosages of glucocorticoid compared with patients who received low dosages. Treatment with cytostatics influenced the rate of infections to a moderate degree. Nephropathy also influenced survival but half of the patients with nephropathy maintained a normal plasma creatinine in spite of the long observation period. 16 per cent of the patients with nephropathy died of kidney failure or are receiving chronic hemodialysis.

Computer-assisted diagnosis of acute azotaemia: diagnostic strategy and diagnostic criteria.

This report describes the diagnostic strategy, cost-effectiveness and diagnostic accuracy of a rule-based, backward chaining diagnostic expert system designed to assist in diagnosing the cause(s) of acute azotaemia. The diagnostic strategy of the expert system seems to be cost-effective compared with that of a renal unit and the diagnostic criteria of the expert system accurately imitate the diagnoses of the renal unit. It is suggested that the expert system is diagnostically reliable and may reduce cost in the diagnostic work-up of patients with acute azotaemia.

Diuresis renography in patients with reduced renal function.

Diuresis renography was performed twice at an interval of one week in 13 uraemic patients without hydronephrosis. In five of the patients, the 51Cr-EDTA clearance was below 10 ml/min x 1.73 m2 for the individual kidney, in eight of the patients between 10 and 25. During the renographies, respectively, 0.5 and 7.5 mg/kg of frusemide was given I.V. at 20 min. Compared with the data from eight normal control patients, the effect of frusemide on the renography curve was very poor and varied much in both groups. Our results suggest that diuresis renography gives no conclusive information about the upper urinary tract in kidneys with a 51Cr-EDTA clearance below 25 ml/min x 1.73 m2, even when the dose of frusemide is increased to 7.5 mg/kg.

Insulin clearance from plasma in type I (insulin-dependent) diabetic patients: influence of glycaemic level.

The influence of the actual glycaemic level on the kinetics of insulin disappearance from plasma was studied in 16 type I diabetic patients. Constant intravenous infusion of insulin (1-5 mU.kg-1.min.-1) was used to achieve different levels of steady state plasma free insulin concentrations, while the blood glucose level was clamped at normoglycaemia, 4.1 +/- 0.1 mmol/l (mean +/- S.E.M.), and mild hyperglycaemia, 8.2 +/- 0.1 mmol/l. The experimentally determined data were compared using a previously validated model of first order kinetics for insulin disappearance from plasma in diabetic patients. At the physiological insulin concentration range the median clearance rate of insulin was 23 ml.kg-1.min-1 (range 16-26) at normoglycaemia and 23 ml.kg-1.min-1 (19-35) at hyperglycaemia (P = 0.45). At supraphysiological levels, insulin was cleared at a lower rate at normoglycaemia than at hyperglycaemia. No correlation was observed between the insulin clearance rate and the duration of diabetes or the haemoglobin A1C level (both Spearman's rho = 0.08). In conclusion, the insulin clearance rate from plasma is independent of the actual glycaemic level and hardly influenced by the long-term glycaemic level in type I diabetic patients.

Cefotaxime disposition pharmacokinetics during peritoneal dialysis.

The pharmacokinetics of cefotaxime and its main metabolite des-acetyl-cefotaxime were studied after a single 1000 mg intravenous dose in 8 patients with end stage renal disease during peritoneal dialysis. Pharmacokinetic parameters were determined by iterative non-linear least squares regression analysis of plasma and dialysis fluid drug concentration curves. Biological half-life of cefotaxime ranged from 2.3 to 8.2 hours and total plasma clearance from 11 to 103 ml/min. (0.11 to 1.7 ml/min/kg b.wt). Only 1.4% to 4.2% of the intravenous dose of cefotaxime was distributed to the dialysis fluid. We conclude that the dosage of cefotaxime to uraemic patients adjusted to the renal function needs no further adjustment during peritoneal dialysis.

Kinetics of insulin disappearance from plasma in cortisone-treated normal subjects.

The effect of glucocorticoid excess on insulin disappearance from plasma was examined in eight normal men during cortisone treatment (50 mg orally twice daily for 4 d) and in the absence of any medication (control) in random order. Constant infusion of insulin (1-5 mU/kg/min) was used to achieve different levels of steady state plasma insulin concentrations; normoglycaemia was preserved by a glucose clamp technique. The experimentally determined data were compared using a previously validated model of saturation kinetics. The amount of glucose required to maintain normoglycaemia during the insulin infusions was significantly less in the cortisone study than in the control study, while the parameter estimates for the kinetics of insulin disappearance from plasma were unaffected by cortisone. Thus, insulin action and insulin kinetics in the steady state are dissociated in normal subjects rendered insulin resistant by short-term cortisone treatment.

Kinetic models for insulin disappearance from plasma in type I diabetic patients.

We have tested whether our previous finding in normal subjects that the disappearance of insulin from plasma obeys saturation kinetics alone also applies to type I diabetic patients. In six long-term diabetic patients steady state plasma insulin concentrations resulting from constant insulin infusion at different rates were compared with the predictions of three models for the kinetics of insulin in plasma. The models allowed the existence of non-saturable (first order equation) or saturable (Michaëlis-Menten equation) mechanisms, or both. The minimal acceptable model included saturation kinetics alone in four subjects and first order kinetics alone in two subjects. The clearance of insulin in diabetic patients, calculated from the best fitting model, was 18.0 (median, range 10.0-23.7) ml X kg-1 X min.-1 versus 25.0 (18.6-47.1) ml X kg-1 X min.-1 in six normal subjects (2p = 0.008). Insulin thus disappears from plasma at a lower rate in diabetic patients than in normal subjects at physiological plasma concentrations.