Hydroxyethyl Starch (HES) commonly is widely used as plasma volume expander. They are often used preoperatively and in cases of hypovolemia.
Hydroxyethyl Starch (HES) commonly is widely used as plasma volume expander. They are often used preoperatively and in cases of hypovolemia.But they may have side effects on renal function [Kumle et al. 1999].Dehne et al. reported that HES infusion to intensive care patients could increase excretion of specific tubular proteins such as alpha1-microglobulin,Tamm-horsfall-protein and brush border enzyme acetyl-beta-glucosaminidase.Animal studies have also shown severe alterations of the proximal tubules after haemodilution with HES[standl et al 1996]. Therefore HES should not be used to treat hypovolemia in Idiopathic nephritic syndrome(INS),though it may be an effective fluid for resuscitation of hypovolemic patients[Palumbo et al 2006].There are few reported cases of HES–induced acute renal failure (ARF) in fluid management of INS patients or acutely ill patients [Adrienne et al .2001, Ding et al. 2003,wang et al. 1996]. We report a 73-year-old woman with mesangioproliferative glomerulonephritis associated reversible ARF with acute tubulointerstitial nephritis(AIN) caused by HES.
A 73-year-old female patient was admitted to hospital because of moderate periorbital and pretibial edema, on October 12, 2007. with no evidence of fatigue ,loin pain, gross hematuria, skin rash or fever. The urine output was 950-1600ml/day. The patient had no history of upper respiratory infection, chronic kidney disease, hypertension, gout ,diabetes or ischemic heart disease. physical examination: Bp 190/100mmHg, T 36.70c, Laboratory findings: WBC 5.5-2.8×103/mm3 ,7% eosinophils,RBC 3.87×106/mm3,hemoglobin 120g/L, Plateletst 226×103/mm3, Na139 mmol/L ,K3.7 mmol/L ,CL 100 mmol/L ,Ca 1.91 mmol/L , P1.31 mmol/L ,ALT 25IU/L,albumin 28.1g/L,CH 8.06 mmol/L,Tg 4.56 mmol/L,HDL 1.76 mmol/L,LDL 4.71mmol/L,blood sugar 4.2mmol/L,BUN 5.3mmol/L,creatinine 115 umol/L, The C3-level was 500g/L and C4-level 130g/L. ASOimmunoglobulins ,ANA, anti-DNA, antiglomerular basement membrane antibodies, ANCA, cryoglobulins, circulating immune complexes, hepatitis B and C viruses ,HIV antibodies were either normal or negative. Urinalysis revealed 4+protein and 1+blood. Proteinuria ranged from 4.37 to 6.0g/daily and renal ultrasound demonstrated mildly enlarged kidneys.ECG findings showed normal sinusal rhythm,chest x-ray was found normal. There was no diabetic retinopathy.
The diagnosis of INS was made and treatment was started with Prednisone ,Tripterygium, Heparin, Dipyridamole, Furosemide and other symptomatic supportive treatment. On the 10th day after admission, HES (500ml of 6% HES were infused once daily ) was added to the previous regimen to treat the intractable hypovolemia, because of hypoproteinemia persisted.On the 14th day ademission,she was noted to have a rising BUN and serum creatinine concentration and she suffered from progressive oliguria. The urine output decreased from normal levels to 250-200ml/day which was associated with rapidly deteriorating renal function. In the following 3 days, creatinine rose to 586umol/l and BUN to 29.5mmol/L.HES-induced ARF was suspected and HES was stopped. She was treated for ARF by hemodialysis and diuretic therapy.At this time a renal biopsy was performed showing a mild diffuse mesangioproliferative glomerulonephritis with moderate interstitial edema containing a severe inflammatory cell infiltrate composed of lymphocytes, monocytes,neutrophils and eosinophils as well as variable tubular ectasia.No acute tubular necrosis was observed. In a few glomeruli synechia and mild epithelial cell proliferation were seen. The blood vessels were normal. No sclerotic glomerular changes were observed.Immunofluorescence showed deposits of IgG, IgM and C3 in the mesangium and in the capillary walles. Thus, the histopathological diagnosis was mesangioproliferative GN with tubulointerstitial changes resembling acute tubulointerstitial nephritis.
ARF with severe tubulointerstitial changes secondary to HES was diagnosed and the original kidney disease was associated to be mesangioproliferative glomerulonephritis. She was treatment with methylprednisolone 0.5g/day for 3 consecutive days. The treatment was continued with Prednisone orally 60mg/day,combinaed with hemodialysis,diuretics and other symptomatic treatment. There was no worsening of the renal function,and subsequently renal function recovered fully. She was discharged and after 6 months of follow-up had a serum creatinine of 112umol/L ,proteinuria had declined to 0.18g/day and she is now doing well.
ARF in patients with NS is a rare and serious complication that has numerous causes.The most common of them are severe hypovolemia ,interstitial edema ,tubularobstruction,altered glomerular permeability and drugs. Although the relationship between HES and ARF appears established by well-documented cases, only a few HES -associated ARF cases have been reported so far [Adrienne et al. 2001, Ding et al .2003,wang et al. 1996]. HES-indused ARF is more frequently among older people, particularly in patients with preexisting renal failure,glomerulosclerosis or diabetes. The highest risk for HES-induced ARF exists during the first 10 days of treatment or when the HES dose is increased[Ding et al. 2003]. The most common clinical presentation of HES-induced ARF is progressive oliguria .Although some of the cases are mild with some patients even fully recovered after the treatment ,HES-induced ARF may be severe and sometimes fatal. in our patient, the renal function and laboratory values were normal during the 10 days before HES infusion and oliguric renal failure developed immediately after exposure to HES. At this same time, the patient was on no other nephrotoxic drugs and had been hemodynamically stable throughout her hospital stay. Therefore,a causal relationship between HES and ARF was considered.
Our patient’s renal function was corrected to normal values while other authors reported that in most cases renal function did not recover fully and that there was a progress to end-stage renal failure. Some patient also died from complications related to persistent severe ARF. Li et al.found that 8 of 13 patients with ARF secondary to HES experienced a progress to end- stage renal disease.
Recently, another paper reported an association between HES-induced ARF and prognosis. Five patients with HES-induced ARF were reported : only in 1 of the patients renal function returned to normal,whereas in 4 patients the renal function did not recover and progressed from acute to chronic renal failure. Moreover, this study has confirmed by renal biopsy that the pathology in patients with ARF due to HES is an osmotic hephropathy [Ding et al .2003].Concerning the prognosis, Severely persistent oliguria, elevated serum creatinine and multiple organ failure are frequentily associated with a poor prognosis[Ding et al. 2003,wang et al .1996]
Our patient did neither suffer from acute tubular necrosis nor from osmotic nephropathy, but from acute tubulointerstitial nephritis which is in accordance with previously previously reported cases of ARF-induced HES [Li et al.2004].
In conclusion,this case suggests that a patient poisoned with HES may have the typical features of oliguric ARF. At should be considered, as a very severe reaction. The mechanism of ARF is not fully understood. Some authors have suggested that possible pathophysiological causes for such a development are most likely to be found in an increased permeability of the glomerular basal lamina[ Waldhausen P,et al 1991]. Whereas other studies have shown that the pathological Substrate of ARF due to HES is an osmotic nephrosis [Ding et al. 2003] or osmotic nephrosis-like lesions[suttner et al. 2004],our findings suggest that an immune disease due to a hapten induced by HES may be a possible factor in the pathogenesis of ARF. Therefore, it is important for clinicians to bear in mind the possibility of ARF due to HES and it has been proposed that ,whenever possible, HES should not be used in INS patients to avoid severe complications.
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