COMPLICATION OF OLIGURIC ACUTE RENAL FAILURE IN PATIENTS TREATED WITH LOW-MOLECULAR WEIGHT DEXTRAN

Abstract

Acute renal failure (ARF) is a well-documented but infrequent complication in patients treated with low-molecular weight dextran (LMWD). We herein report 3 cases of oliguric ARF following the administration of dextran-40. One case developed ARF totally after 1.200 g of LMWD administration. In contrast, two cases having increased serum creatinine developed oliguria despite the acceptable therapeutic doses (totally 450 and 650 g). Contrast media was also co-administered in these patients. Plasma exchange (PE), double filtration plasmapheresis (DFPP), or continuous hemodiafiltration (CHDF) but not hemodialysis (HD) reduced circulating dextran concentrations by 35–44% during a single session. All patients completely recovered from ARF by 14–32 days after the treatment. Our cases suggested that radiocontrast could predispose to the development of LMWD-induced ARF especially in patients having pre-existing renal dysfunction. In addition, PE, DFPP and CHDF afforded a beneficial effect for removing accumulated LMWD from the circulation.

• Dextran
• Oliguria
• ARF
• Radiocontrast
• Plasma exchange
• Continuous hemodiafiltration

INTRODUCTION

Low-molecular weight dextran (LMWD), dextran-40, is clinically used as plasma expander and anticoagulant in open-heart surgery, systemic hypotension and severe peripheral vascular disease. In normal subjects, dextran is considered relatively safe, and 70% of an intravenous dose of LMDW is rapidly excreted from the kidney within 12 h. Acute renal failure (ARF) following dextran administration is a rare but serious complication [1-11]. However, the clinical manifestations and treatment of dextran-induced ARF remain to be fully understood. We herein report 3 patients who complicated of oliguric ARF following the dextran-40 treatment.

CASE HISTORIES

The case histories and characteristics of our patients are summarized in Table 1. All patients were transferred to our department because of the development of ARF. In case 1, totally 1.200 g of LMWD, which exceeded therapeutic range, was administered for the treatment of right sudden deafness. She had well-controlled diabetes and hypertension during the recent 7 and 13 years, respectively. At the beginning of the treatment, her renal function was normal. Eleven days after the treatment (100 mg/day), she suddenly complained of oliguria and severe dyspnea, and finally became drowsy. She was diagnosed as having ARF due to LMWD on 12 hospital days.

Table 1. Clinical Characteristics of the Patients with Dextran-induced ARF

Patient Age/Sex Disease Complications	1 75/F Sudden Deafness DM, HT	2 65/M Cerebral Infarction IHD	3 58/M Cerebral Infarction IHD
Total doses of LMWD (g)	1,200	650	450
Duration of LMWD treatment (days)	12	8	5
Duration for ARF onset (days)	11	8	5
Scr/BUN (mg/dL)
Baseline	1.0/11	2.1/30	1.4/22
Peak	9.5/84	9.3/76	3.9/59
Urine volume at onset (mL/day)	200	130	80
Duration of oliguria (days)	13	6	1
Pulmonary congestion	(+)	(+)	(+)
Treatment	HD: 6 days	HD: 10 days	CHDF: 1 day
	PE: 2 days	DFPP: 2 days
Duration for recovery (days)	32	39	14

Abbreviations are ARF, acute renal failure; DM, diabetes mellitus; HT, hypertension; IHD, ischemic heart disease; LMWD, low-molecular weight dextran; Scr, serum creatinine; BUN, blood urea nitrogen; HD, hemodialysis; PE, plasma exchange; DFPP, double filtration plasmapheresis; CHDF, continuous hemodiafiltration.

In case 2 and 3, the patients developed ARF despite the acceptable therapeutic doses of dextran-40 (totally 450 and 650 g over 5 to 8 days). At admission, both patients had ischemic heart disease with mild renal dysfunction. The treatment of LMWD (100 mg/day) was soon started for the treatment of acute cerebral infarction. Angiography was also performed for the diagnosis of cerebral infarction at the first and second hospital day in both patients. Five and eight days following the administration of dextran-40, oliguria became evident. Both patients also had marked pulmonary congestion at the onset of oliguric ARF.

EFFECT OF BLOOD PURIFICATION FOR DEXTRAN-INDUCED ARF

After the diagnosis of oliguric ARF, all patients soon received blood purification because of resistance to diuretic therapy including massive furosemide injection (160 mg). In case 1, totally 6 sessions of hemodialysis (HD) and 2 sessions of total plasma exchange (PE) were conducted during 18 days. Replacement of 2.5 L fresh frozen plasma was used to keep plasma volume for PE treatment. In case 2, totally of 10 HD sessions and 2 double filtration plasmapheresis (DFPP) sessions were performed during 23 days. At the time of DFPP, totally 2.0 L of 2.5% human albumin was constantly infused. In case 3, only one session of continuous hemodiafiltration (CHDF) was done for 6 h to remove excess fluid (2.7 L), and his urine output was soon restored just after the treatment. All patients recovered form oliguria 13, 6 and 1 days after the beginning of treatments, respectively. Serum creatinine levels were gradually returned to basal values over 32, 39 and 14 days, respectively (Table 1).

Changes of circulating dextran concentrations during a single session were shown in Table 2. PE and DFPP reduced serum dextran levels by 43 and 44% during a single session in case 1 and 2. Effluent fluids during DFPP treatment contained a rich dextran content. CHDF also reduced serum dextran level by 35% in case 3. The effluent contained a high concentration of dextran (4.74 mg/mL), and totally 23.7 g of dextran was removed from the circulation during 6-hour CHDF therapy. This value probably reflected 35% removal of estimated dextran content in the circulation (67.7 g). In contrast, a single HD session using conventional cellulose membrane did not change serum LMWD levels.

Table 2. Effects of Blood Purification of Removal of Circulating Dextran

		Serum dextran levels (mg/mL)
Case	Treatment	Pre	Post	% Decrease of dextran (%)	Effluent dextran (mg/mL)
1	PE	8.01	4.53	43	ND
	HD	5.13	4.56	11
2	DFPP	4.62	2.61	44	5.28
	HD	4.42	4.91	−15
3	CHDF	24.47	15.83	35	4.74

Abbreviations are PE, plasma exchange, HD, hemodialysis; DFPP, double filtration plasmapheresis, CHDF, continuous hemodiafiltration and ND, not determined.

In case 3, we measured serum dextran values during the 5 successive days after the initial CHDF treatment. Serum dextran values were spontaneously and gradually decreased to 12.49, 6.95, and 5.66 mg/mL at 2, 3 and 4 days after the treatment despite the stop of CHDF treatment. Urine samples obtained at day 3 and 4 also contained 7.52 and 6.50 mg/ml of dextran, so the estimated urinary dextran excretion became 18.7 and 7.9 g per day, respectively. Five days after the CHDF treatment, serum creatinine and dextran values were reduced to 2.2 mg/dl and 1.76 mg/mL.

DISCUSSION

Dextran-40 is a polysaccharide of an average molecular size of 40.000 (range from 10.000 to 80.000). Clearance of dextran from the kidney is dependent on its molecular size. Smaller fractions of dextran-40 (molecular weight, 14.000–18.000) are readily filtered through glomerular capillary membranes, but larger fractions over 50.000 molecular weight are not excreted until they are eventually metabolized.

The complication of ARF following LMWD administration has been demonstrated especially in patients with ischemic vascular disease over the past 30 years (1–11). Feest (2) first noticed that administration of 100–600 g of LMWD during 2–5 days caused oliguric ARF only in patients with systemic ischemic disorders. Experimental studies [12-13] also demonstrated that anuria easily occurred when renal perfusion pressure was reduced by renal artery stenosis, aortic constriction, or hemorrhagic hypotension. Recently, Biesenbach et al. [[9]] found that 10 (4.7%) of 211 patients with acute ischemic stroke developed ARF following the LMWD administration (50 or 100 g/day) for 3–6 days. They found that the incidence of dextran-induced ARF was significantly higher in patients with glomerular filtration rate below 30 mL/min/1.73m². In our patients, except for one patient who received excess LMWD (case 1), two patients already had increased serum creatinine values at the beginning of LMWD infusion. It follows from these findings that the patients having renal dysfunction have a greater risk for the development of dextran-induced ARF.

In our patients, contrast media was co-administered at the same time of dextran infusion. Because contrast media is a well-documented renal vasoconstrictor, the agent-induced secondary renal ischemia may further predispose to the development of dextran-induced ARF. In addition, the abundant existence of intratubular radiocontrast and dextran may generate extremely high-viscosity urine, subsequently inducing tubular plugging by casts and a decrease in urine output [[13]]. In agreement with our cases, Kurnik et al. [[8]] reported a patient who developed ARE following the co-administration of radiocontrast and a small dose of dextran-40 (totally 90 g).

In the present study, the treatment with PE and DFPP lowered circulating dextran levels by 43 and 44% during a single session. Serum half-lives of low-molecular weight fractions (14.000–18.000) and middle fractions (40.000–50.000) are 15 min and 7.5 h. Since serum dextran levels were decreased from 8.01 to 4.53 mg/mL by PE and from 4.62 to 2.61 mg/mL by DFPP within 2 to 3 h, these falls seem to be much greater than those expected based on serum half-life of middle-molecular weight dextran. In addition, we confirmed the presence of a rich amount of dextran in the DFPP disposal effluent. These findings convincingly suggested that PE and DFPP have a potential benefit for the removal of dextran, as described previously [[3]], [7-8]. In contrast, HD procedure itself did not change serum dextran levels during a single unit in both cases (Table 2).

It remains undetermined whether the removal of circulating dextran was responsible for the improvement of renal function in our cases. However, we noticed that a prompt increase in urine output had occurred shortly after the removal of circulatory dextran in case 3. In addition, once diuresis occurred, circulating dextran was easily excreted into urine, and renal failure was eventually restored 14 days after the onset of ARF. Moran and Kapsner [[5]] speculated that a rapid removal of dextran from the circulation could decrease the plasma colloid (negative) oncotic pressure, which might increase the transglomerular (positive) hydraulic pressure that promotes fluid movement into Bowman's space, and generate urine promptly.

The beneficial effect of removal of circulating dextran has been already demonstrated. In the previous cases [[3]], [7-8], PE and DFPP completely recovered dextran-induced ARF similar to the present cases. In contrast, HD or peritoneal dialysis alone did not provide sufficient recovery from kidney failure [[2]], [[4]]. Additional case studies are needed whether a prompt removal of circulating LMWD may truly fasten recovery of renal function in dextran-induced ARF.

In summary, we experienced 3 cases of dextran-induced oliguric ARF. In 2 cases, radiocontrast was concomitantly administered with dextran-40. Treatment with PE, DFPP, and CHDE reduced circulating dextran concentrations by 35–44% during a single session, but HD did not. Our cases suggested that co-administration of dextran and contrast media readily predisposed to the development of ARF especially in patients with pre-existing renal dysfunction. In addition, a rapid removal of circulating dextran by PE, DFPP or CHDF may be effective for restoring urine output and renal function.