The acute flank pain syndrome: a common presentation of acute renal failure in young males in Iceland.

Sir,

In 1987, the non-steroidal anti-inflammatory drug (NSAID) suprofen was withdrawn from the market due to ∼400 cases of the so-called ‘acute flank pain syndrome’ (AFPS) which was ascribed to the drug [1]. AFPS, characterized by severe flank pain, acute renal failure and recovery within 1 or 2 weeks, was most common in young males [2]. After withdrawal of suprofen, only a few reports have been published, associating AFPS with ingestion of other types of NSAIDS, binge drinking or both [3-5]. In Iceland, the nephrologists have been aware of AFPS since the mid-1990s. By now, typical patients are managed with analgesics and by observation after minimal investigation.

We screened the records of patients aged 18–41 years who received the diagnosis acute renal failure at Landspitali University Hospital during the period 1998–2007, and patients with AFPS were identified. AFPS was defined as severe flank or abdominal pain upon admission in combination with acute renal failure (serum creatinine concentration >50% increase of baseline or upper reference range), both features unexplained except for the possible intake of an NSAID, ethanol or both. Information about total and over-the-counter sales of ibuprofen and diclofenac during the study period was collected.

There were 106 cases of acute renal failure. Of these, 21 (20%) had AFPS which amounts to an average incidence of 20.1/million/year. The incidence increased during the study period (Table 1). None of the AFPS patients had a history of kidney disease. Eighteen patients were males, and the median age was 26 (18–35) years. There was information about recent consumption of NSAIDs in 15 patients (ibuprofen in 8, diclofenac in 2, both in 2 and unknown type in 3), ethanol in 15 patients, either in 20 patients and both in 9 patients. The laboratory results are shown in Table 1. The sales figures of the NSAIDs were high, and they increased during the study period, especially the over-the-counter sales of ibuprofen (Table 2).

Table 1

The year of diagnosis and the laboratory results of the patients who sought assistance in the emergency room at Landspitali University Hospital because of acute flank pain syndrome

Year	Serum creatininea (µmol/L)		CRP (mg/L)	Urine density (g/mL)	Urine protein	Urine red cells (per hpf)	Urine white cells (per hpf)	US kidneys	Kidney biopsy
	Max	Follow-up (day)
1998	179	122 (7)		1.007	+	10–25	1–2	↑echo	normal
1998	238	181 (6)		1.007	+	2–5	2–5	↑echo	ATN
2000	178	137 (5)		1.006	+	5–8	3–5	↑echo
2001	236	127 (10)	25	1.006	+	5–10	0–2
2003	330	99 (13)		1.010	+++	5–10	1–2	↑echo	ATN
2003	215	97 (7)	25	1.010	+++	1–2	1–2	normal
2004	256	112 (7)	38	<1.005	+++	0–1	2–5	↑echo
2004	189		56	1.005	+++	0–2	2–5	normal
2005	251	108 (11)	14	<1.005	++	1–2	0–5	↑echo
2005	243	100 (4)		<1.005	++	0	0–1
2005	256	204 (4)	22	1.010	+++	2–5	2–5	normal
2005	166	93 (24)	25	<1.005	(+)	5–10	2–5
2006	137	85 (10)	6	1.020	−	0	5–10	normal
2006	202	104 (20)	80	1.010	−	0–1	2–5	↑echo
2006	427	158 (5)	<3	1.025	+++	5–10	1–2	↑echo
2007	252	104 (6)		<1.005	−	2–5	1–2
2007	381	207 (6)	24	<1.005	+++	1–2	1–2
2007	261	76 (15)	21	1.015	+++	5–10	10–25
2007	529	97 (23)	30	1.020	+++	2–5	2–5
2007	320	85 (13)	25	1.015	++	0–1	0–1	↑echo
2007	286	97 (79)	51	1.010	−	1–2	0–1

Gaps indicate missing information.

CRP, C-reactive protein; hpf, high-power field; US, ultrasonography; ↑echo, increased echogenicity; ATN, acute tubular necrosis.

aReference range 100 µmol/L for males and 90 µmol/L for females.

Table 2

The sales of ibuprofen and diclofenac in the Nordic countries according to the Icelandic Medicines Agency (Iceland), the Danish Medicines Agency (Denmark), Folkhelseinstituttet (Norway) and Apotekens Service AB (Sweden)

Country	Year	Ibuprofen total	Ibuprofen OTC	Diclofenac total	Diclofenac OTC
Iceland	1998	12.8	4.2	14.5
Iceland	1999	14.8	5.7	18.0
Iceland	2000	16.8	7.2	17.5
Iceland	2001	20.0	8.7	16.8
Iceland	2002	25.3	14.1	17.2	0.2
Iceland	2003	30.7	19.5	16.9	0.2
Iceland	2004	33.8	21.6	17.3	0.2
Iceland	2005	35.1	22.0	20.1	0.7
Iceland	2006	36.0	22.6	20.3	0.6
Iceland	2007	29.8	19.0	20.7	1.2
Denmark	2007	21.0	6.2	8.2
Norway	2007	16.8	9.8	9.6
Sweden	2007	7.1	5.3	4.2	0.5

The sales are given in defined daily doses/1000 inhabitants/day.

OTC, over-the-counter.

This retrospective study underestimated the countrywide incidence of AFPS; an unknown number of patients who sought the advice of their general practitioners were never admitted to the hospital since the consultant nephrologist recognized AFPS upon description. In spite of this, the study revealed the largest body of material of AFPS that has been reported since the suprofen experience. Moreover, the study showed that AFPS is a common presentation of acute renal failure in young adults in Iceland.

The scarcity of reports indicates that AFPS is uncommon. However, AFPS may be underreported. The incidence of AFPS is high in Iceland which can possibly be explained by heavy consumption of NSAIDs in a country where binge drinking is common. There may be a causal relationship between the simultaneous increases in the incidence of AFPS and the over-the-counter sales of ibuprofen.

There is uncertainty of whether the kidneys recover completely or whether there is residual renal damage after AFPS.

Conflict of interest statement. None declared.