Nephron 17: 136-143 (1976)

Glycolipid Modifications during Peritoneal Dialysis in Patients with Chronic Renal Failure U. Z uliani, A. N ovarini, A. Bonetti, S. C aronna, P. C oruzzi and A. C avatorta1 Istituto di I Clínica Medica generale e Terapia medica (Direttore: Prof. C. B ianchi) e Istituto di Semeiotica medica (Direttore: Prof. A . B orghetti), Universitá degli Studi di Parma, Parma

Key Words. Glycolipid metabolism ■Peritoneal dialysis • Chronic renal failure Abstract. Ten patients with progressive CRF were studied for the major indices of gly­ colipid metabolism during the first application of peritoneal dialysis. From the 2nd hour the concentration of dialysis fluid is 4.5 g%, while the electrolyte content is unchanged. During treatment a constant increase of glycemia and insulinemia with a fall of plasma-free fatty acids and serum triglycerides was observed. The authors attribute such modifications to hyperglycemia and consequently to the high glucose of the dialysis bath.

Introduction Our knowledge of the glycolipid metabolism in chronic renal failure has been enriched in the last few years by the contributions of many authors [2,5, 11], Interest in these investigations has increased not only because of thorough examination of some poorly known physiopathologie aspects but also because of the practical implications which may be derived [3,10]. In our research on the glycolipid metabolism in the course of chronic uremia, we were able to evaluate the modifications induced by some stimuli [15,19,22] or present in some particular therapeutic conditions, such as long­ term 3-week extracorporeal dialysis [21] and short-term dialysis on alternate days [14], The indication for peritoneal dialysis in some patients with chronic renal failure has given us the opportunity to go thoroughly into some aspects of 1 We wish to thank Miss R omana G ardini for her technical assistance.

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Received: May 26, 1975; accepted: August 28, 1975.

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Table I. Changes induced in some blood constituents and body weight by the first peritoneal dialysis (mean of 10 patients)

Body weight, kg BUN, mg% Blood creatinine, mg% Serum potassium, mEq/1 Serum chloride, mEq/1 Serum sodium, mEq/1 Hematocrit, % Hemoglobin, g%

Before

After

70.4 320 12.5 5.1 110 135 20.5 7.0

68.1 195 10.5 4.0 103 140 21 7.5

the glycolipid metabolism, also in view of the particular technique of this treatment. In fact, during peritoneal dialysis, unlike in hemodialysis, the fluid perfuses the peritoneal cavity, heparin is not used and each application lasts at least 24 h. The bath composition is also different; it contains sodium lactate in place of sodium acetate, and the glucose concentration can be varied accord­ ing to indications emerging during the treatment. We think, therefore, that a study during peritoneal dialysis, due to the particular character of this treatment, may contribute useful elements to the understanding of some physiopathologie aspects not commonly known in the course of this therapeutic procedure [18] and would help also in clarifying some phenomena noted in previous research.

Our experiments were carried out on ten patients with progressive chronic oligoanuric renal failure, consequent to various kinds of nephropathies. The creatinemia values are all above 12 mg% and azotemia to 3 g%. In table I the mean values ± SD are given for the major hemochemical indexes and body weight, before and after dialysis. Patients were aged between 28 and 60 years. We expressly chose patients that did not have familial diabetes or presented altered liver function tests, or showed a carbohydrate intolerance (evaluated by a glucose load curve). The study was carried out in all patients during the first dialysis, and each application was continued at least 24 h. The technique of direct peritoneal puncture was used. Treatment was started with a dialysis solution, containing 140 mEq/1 N a; 4 mEq/1 Ca; 1.5 mEq/1 Mg; 101 mEq/1 Cl; 45 mEq/1 lactate; 3-4 mEq/1 K, and 1.5 g% glucose. From the second or third application (approximately 1 h from the beginning of treatment) the glucose concentration was in-

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Material and Methods

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Table II. Mean values ± SD of blood glucose, FFA, TG, and blood insulin before and during peritoneal dialysis

Blood glucose, mg% FFA, p.Eq/1 TG, mg% Blood insulin, pU/ml

Basal

During peritoneal dialysis

values

1h

2h

3h

83 ±13 473+62 165±35 16±10

147±40 429 ±108 168 ±30 29 ±16

201 ±52 378±89 171 ±39 43±18

222 ±52 219±72 375± 121 330±54 150±34 150±54 56±22 63 ±15

6h

12 h

18 h

24 h

205 ±50 312 ±70 146±46 63 ±18

212±83 315 ±66 120±30 45 ±20

205 ±83 305±115 131 ±50 40±16

creased to 4.5 g%, the other components remaining unchanged. Each change of 2 liters of dialysis solution represents an infusion time of 10 min, a permanence time in the peritoneal cavity of 5-7 min, and a drainage time of approximately 30-40 min. The total amount of fluid used varied from 50 to 60 liters for a 24-hour dialysis. As a rule blood was taken before and during dialysis, at the 1st, 2nd, 3rd, 6th, 12th, 18th and 24th hour. For the entire dialysis period the patient was kept fasting. Evaluation of the parameters (glycemia, free fatty acids (FFA), triglycerides (TG), and insulinemia) was done by an already described procedure [22].

Results

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Mean values ± SD at the evaluation times of glycemia, insulinemia, FFA, and TG are given in table II. Glycemia begins with mean values within the normal range (83 ± 13 mg%), reaches the maximum (222 ± 52 mg%) 3 h after the beginning of dialysis application, and remains constant at values above 200 mg% for the entire length of the treatment (fig. 1). Insulinemia behaves similarly to glycemia. From basal mean values within the normal range (16 ± 10 nU/ml) it reaches the peak at the 6th hour (63 ± 15 pU/ml) even if, at the 3rd hour, values are already very high (56 ± 2 2 pU/ml) and nearly superimposable on the values recorded at later times; at the 12th hour and beyond, a slight but constant decrease is observed. The mean values always remain, however, clearly higher than the basal ones and closer to those reached during the course of treatment (fig. 1). The mean basal values of plasma-FFA and serum TG are also in the normal range (473 ± 62 ¡¿Eq/1, and 165 ± 35 mg%, respectively). Nevertheless, the behavior of these parameters differs in the following phases. FFA, in fact, show a rapid decrease to the 3rd hour at which time it becomes slower, and more constant, to stabilize at about 300 ¡¿Eq/1 by the

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Dialysis, h

Fig. 1. Modifications of glyccmia and insulinemia during peritoneal dialysis.

end of treatment. TG, on the contrary, remain substantially unchanged in the first 2 h and then decrease at the end of treatment, reaching the lowest mean levels at the 18th hour (120 ± 30 mg%) (fig. 2).

Our research points out a series of metabolic modifications in which the literature is contradictory and not very complete [1,12,13,18]. In fact, during peritoneal dialysis, performed as described, we have ob­ served on the one hand an obvious increase in glycemia and insulinemia which is constant for the duration of treatment, and on the other hand, important changes in plasma-FFA and serum TG. The hyperglycemia is a consequence of the high amounts of glucose present in the perfusion fluid [1], It represents a stimulus to insulin release [8] which in our experience behaves similarly, even if not constantly, to the glycemia as reported also by M ir o u z e et al. [13], The modifications observed in the plasma-FFA and in serum TG may be due to certain components of the dialysis bath.

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Discussion

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Plasm a -FFA, pEq/l

500

-

400

-

300200

-

T—

i— i—

0

1

2

------------------1--------------------1------------------- r

3

6

12

16

24

TG, mg7.

200

160 120

-

n — i— i— r-r f —i---------- 1----------- 1-----------r 0

1

2

3

6

12

18

24

Dialysis, h

Fig.2. Modifications of plasma-FFA and serum TG during peritoneal dialysis.

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We think, however, that the predominant effect must be attributed to glucose and hyperinsulinemia and consequently to the high glycemic values. In fact, at least with regard to the influence of FFA on the acetate metabolite, analogous to sodium lactate - and used for the same purpose, the acidosis correction - reports in the literature are at variance: no effect [4], slight in­ crease [20]. Evidently, the FFA decrease we observed is imputable to hyper­ insulinemia which at any rate can mask a possible interference of lactate. The TG mean basal values in uremic patients on maintenance treatment are within normal range, at least in the case of the patients in our study; in disagreement with the reports of Bierman [5] and R eimold et al. [18] our values, however, are superimposable on those found by Bagdade [2] who considered them to be pathologic. In the course of chronic hemodialysis treatment we have found, however, a hypertriglyceridemia in basal condi­ tions [16]. We think it important to differentiate between two periods in the TG line, an initial one (for the first 2 h) in which it does not undergo important changes even in the presence of simultaneously marked modifications of the other parameters considered, and a second in the following hours in which a TG decrease is noted, while a marked decrease of FFA persists.

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The difference in behavior can be interpreted as being due to the acute effect of hyperinsulinemia [9] in the first hours, more evident at the hepatic level, with esterification of FFA and synthesis of TG [17]. In the second period, the phenomenon becomes more complex and not easily interpreted. It is possible that insulin exercises its action simultaneously in the liver and in the fatty tissue [2,6,11] with apposing effects on the TG serum concentra­ tions. We think that the hormone action, in this period, may take place in the fatty tissue, with greater esterification of plasma-FFA and hydrolysis of serum TG. Analogous behavior, on the other hand, has been reported by J onhs and A rky [9] in the normal during prolonged administration (24 h) of insulin.

Conclusions Our observations prove that in the course of peritoneal dialysis numerous and clear modifications in the glycolipid metabolism occur. During treatment, at least in our experimental conditions (dialysis fluid containing 4.5 g% of glucose and 45 mEq/1 sodium lactate), it is likely that changes of glycemia, insulinemia, FFA, and TG are attributable mainly to glucose and tire hyperinsulinemia caused by it. The evaluation of these modifi­ cations is different during dialysis, and in our opinion two different periods can be recognized: a first, initial period (2 h approximately) with hyperglycemia, hyperinsulinemia, FFA decrease and poor TG changes in which it is probable that the insulin acts mainly at the hepatic level; a second, longer period (from the 12th to the 24th hour) with an increase in glycemia and insulinemia, and a decrease in the FFA and TG in which the insulin action becomes more evident and prevails at the fatty tissue level. We think that a study of the phenomenon, pointed out in this research, may be of interest for the knowledge of some not commonly known physiopathologic aspects, while it is undoubtedly, of minor interest for the possible clinical implications due to the fact that peritoneal dialysis, unlike hemo­ dialysis, now has limited indications in the treatment of chronic renal failure.

1 A ndersson, G.; B ergquist-Poppen, M.; B ergstrom, J.; C ollste, L.G., and H ult man, E.: Glucose absorption from the dialysis fluid during peritoneal dialysis. Scand. J. Urol. Nephrol. 5: 77-79 (1971).

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References

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2 Bagdade, J.D .: Lipemia, a sequela of chronic renal failure and hemodialysis. Am.J. clln. Nutr. 21: 426-429 (1968). 3 Bagdade, J. D. : Disorders of carbohydrate and lipid metabolism in uremia. Nephron 14: 153-162(1975). 4 Balasse, E.O.: Interaction of insulin, ketone bodies and free fatty acids in the regulation of peripheral utilization of substrates; in M alaisse and P arart Diabetes, pp. 231-240 (Excerpta Medica, Amsterdam 1974). 5 B ierman, E. L. : Abnormalities of carbohydrate and lipid metabolism in uremia. Archs intern. Med. 126: 790-792 (1970). 6 C arlson, L.A. and Bally, P.R.: Inhibition of lipid mobilization; in R enold and C ahill Adipose tissue, p.557 (Williams & Wilkins, Baltimore 1965). 7 D ’O nofrio, F.; F rascolla, N. e T orella, R.: in II diabete mellito. Aspetti fisiopatologici e clinici, p.64 (Idelson, Napoli 1973). 8 G oodner, C.J.; C onway, M.J., and W errbach, J.H .: Control of insulin secretion during fasting hyperglicemia in adult diabetics and in nondiabetic subjects during infusion of glucose. J. clin. Invest. 48: 1878-1886 (1969). 9 J ones, D.P. and A rky, R .A .: Effects of insulin on triglyceride and free fatty acid metabolism in man. Metabolism 14: 1287-1293 (1965). 10 L idner , A.; C harra , B.; S herrard, D.J., and Scribner, B.H.: Accelerated athero­ sclerosis in prolonged maintenance hemodialysis. New Engl. J. Med. 290:697-701 (1974). 11 L osowsky, M.S. and K enward , D .H .: Lipid metabolism in acute and chronic renal failure. J. Lab. clin. Med. 71: 736-743 (1968). 12 M igone, L. e Borghetti, A.: Aspetti fisiopatologici e clinici dell’insufficienza renale. Relaz. 69° Congr. Med. Int. It., Roma 1968 (Pozzi, Roma 1968). 13 M irouze, J.; M ion , C.; O rsetti, A. et J ullien, C.: L’équilibre insulinémique encours de péritonéo-dialyse périodique dans l’insuffisance rénale chronique. J. Urol. Nephrol. 73: 790-801 (1967). 14 N ovarini, A.; Bonetti, A.; Bruschi, G.; C aronna, S.; M ontanari, A.; Rossi, E. e Z uliani, U.: Aspetti del metabolismo glicolipidico nell’insufficienza renale. Effetti di applicazioni dialitiche con tempi brcvi, 3-4 ore, a giorni alterni. Minerva med. 66: 473-477 (1975). 15 N ovarini, A.; Z uliani, U.; Borghetti, A.; Bruschi, G .; G hinelli, L.; M ontanari, A., and R astelli, P.: Features of glycolipid metabolism in chronic renal insufficiency. The effects of intravenous glucose loading. Panminerva med. 16: 266-270 (1974). 16 N ovarini, A.; Z uliani, U.; Strata, A.; Borghetti, A., and M igone, L.: Effects of different dialysis time on some aspects of the metabolism of carbohydrates and lipids. Proc. 11th Congr. EDTA, Tel Aviv 1974, pp.374-382 (Pitman, London 1975). 17 R eaven, G .M .; Lerner, R.L.; Stern , M.P., and F arquhar, J.W .: Role of insulin in endogenous hypertriglyceridemia. J. clin. Invest. 46: 1756-1767 (1967). 18 Reimold , G .M .; K attermann, R. und Q uellhorst, E.: Serumlipide bei chronischer Niereninsuffizienz und deren Beeinflussung durch Glucose und Sorbit während der Peritonealdialyse. Arch. klin. Med. 216: 384-401 (1969). 19 Strata , A.; Z uliani, U.; N ovarini, A. e B orghetti, A.: S u alcuni aspetti del meta­ bolismo glicolipidico in corsodi insufficienza renale cronica. Atti 5 Congr.Naz.Soc.Ital. Diabetologia, Novara-Belgirate 1974, pp. 699-705. 20 T saltas, T .T . and F riedman, E.A.: Plasma lipid studies of uremic patients during hemodialysis. Am. J. clin. Nutr. 21:430-435 (1968).

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Dr. U. Z uliani, I Clínica Medica dell’Universitá degli Studi, Ospcdali Riuniti, 1-43J00 Parma (Italy)

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21 Z uliani, U.; B oneiti, A.; B ruschi, G.; C aronna, S.; M ontanari, A.; Pisani, E. e N ovarini, A.: Aspetti del metabolismo glicolipidico in corso di insufficienza renale crónica. Effetti di applicazioni dialitiche con tempi lunghi (7-12 ore a ritmo trisettimanale). G. Clin. med. 54: 803-813 (1973). 22 Z uliani, U.; N ovarini, A.; B orghetti, A.; B onetti, A.; B ruschi, G.; C onsigu , P. e M ontanari, A.: Aspetti del metabolismo glicolipidico nella insufficienza renale crónica. Effetti del carico orale di glucosio. Minerva nefrol. 20: 28-34 (1973).

Glycolipid modifications during peritoneal dialysis in patients with chronic renal failure.

Nephron 17: 136-143 (1976) Glycolipid Modifications during Peritoneal Dialysis in Patients with Chronic Renal Failure U. Z uliani, A. N ovarini, A. B...
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