Is the sauna a common place for experiencing acute renal failure?
Nina Hofmann1,
Rüdiger Waldherr2 and
Vedat Schwenger1
1 Department of Nephrology, University of Heidelberg2
Gemeinschaftspraxis für Pathologie
Heidelberg, Germany
Email: vedat_schwenger{at}med.uni-heidelberg.de
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Case
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A 29-year-old African-American male was referred to the intensive care unit with acute renal failure. Two days before admission he had collapsed twice after several visits to a sauna. Similar attacks had occurred 2 months before under comparable conditions. The patient denied drug abuse. Upon arriving at hospital he complained of myalgia, especially in the lower extremities, and abdominal pain. His past medical history included osteoarthritis, which was treated with non-steroidal anti-inflammatory drugs.
At presentation, blood pressure was 130/80 mmHg and pulse rate was 76 beats min1. The patient had an athletic stature (180 cm, 64 kg). Physical examination was remarkable for oedematous tumescence of the right leg and pain in the right abdomen and flank region. Urine excretion was diminished to 250 ml/24 h. A standard echocardiograph revealed no pathological changes. Creatine kinase (CK) values were remarkably elevated (initial laboratory data are presented in Table 1). Urinalysis showed proteinuria (>300 mg/dl) and haematuria [200 red blood cells (RBCs)/µl]. On microscopic examination, >50 RBCs per visual field were seen. Serological tests for viral infections (including HIV) were negative. Urinary drug screen yielded negative results. Subsequent abdominal sonography showed hepatomegalia with signs of steatosis. Renal sonography confirmed acute renal failure. Normal muscle action potentials were indicated by electromyogram. Deep vein thrombosis of the right leg was excluded by colour Doppler sonography. Over the course of the patient's hospitalization, CK decreased to 4605 U/l. Myalgias gradually resolved. Creatinine peaked at 12.5 mg/dl and returned to 3.8 mg/dl. Dialysis was performed 17 times and continued until the patient's last day in hospital. Haemoglobin reached a nadir of 7.6 g/dl; anaemia was treated with darbepoetin alpha 20 µg/week. After 23 days, the patient was discharged in a stable condition, but was still dialysis-dependent. Since renal function was improving rather slowly, renal biopsy was performed, showing glomerular hypertrophy, slight tubular atrophy and moderate arteriolosclerosis (Figures 1 and 2). Immunohistology yielded negative results; no immune complex deposits were detectable. There was no evidence of either glomerulonephritis or interstitial nephritis.

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Fig. 1. Increase in glomerular size with diameters up to 350 µm and otherwise normal glomerular tufts. Periodic acidSchiff stain.
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Fig. 2. Increase in glomerular size with diameters up to 350 µm and otherwise normal glomerular tufts. Trichrome stain.
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Questions
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- What is the explanation for this patient's immense CK level?
- What caused the acute renal failure?
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Answer to the quiz on the preceding page
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In our case, rhabdomyolysis occurred after severe dehydration due to several visits to the sauna. Dehydration and local ischaemia induced an acute vaso-occlusive crisis in this patient with known sickle cell trait (SCT). This resulted in muscle damage and CK level rising to an extreme of 476 000 U/l, with acute renal failure as the consequence.
SCT is a heterozygous condition characterized by the presence of haemoglobin AS. Approximately 810% of the African-American population has SCT. In our case, haemoglobin electrophoresis revealed HbA 51.24%, HbS 38.7%, HbF <0.01% and HbA2 3.53%, consistent with SCT. In general, SCT is a benign condition that does not affect the longevity and health of the individual. Nevertheless, carriers are capable of developing any and all types of vascular occlusive lesions that have been observed in patients with sickle cell anaemia. Sickling occurs as a result of haemoglobin S forming polymeric fibres when RBCs are exposed to acid environments, increased osmolality, dehydration and hyperthermia [13], conditions which shift the oxygen-binding curve to the right. Numerous authors have reported exercise-induced rhabdomyolysis and subsequent renal failure in subjects with SCT, primarily in military medical literature in reference to recruits of African origin [46].
Sickle cell nephropathy, however, is not only the consequence of a crush syndrome caused by massive decay of muscular tissue. Sickle cell crisis in patients with SCT also leads to functional disturbances and anatomical aberrations in the kidney itself [7,8]. The hypoxic, acidotic and hyperosmolar environment of the medulla promotes sickling of erythrocytes and, thus, causes disruption of normal blood flow patterns, resulting in impaired function of the loop of Henle (functional papillectomy). Obliteration of the vasa recta interferes with countercurrent exchange. Clinically, patients demonstrate an inability to concentrate urine. In addition, other renal functions that are primarily performed in the medulla, including distal hydrogen and potassium secretion, are also found to be impaired. Sickle cell patients are unable to lower their urine pH to <5. Hyperkalaemia does not usually occur in sickle cell patients despite reduced potassium excretion, suggesting an increased intracellular shift, probably due to ß2 adrenergic stimulation [8]. In contrast to distal defects, proximal tubular function appears supranormal, as evidenced by increased reabsorption of phosphorus and increased secretion of uric acid. Haematuria, both microscopic and gross, is another common finding in SCT. Sickling of erythrocytes leads to microthrombi formation and ischaemic necrosis, which, in turn, can cause structural damage resulting in haematuria. Another sign of glomerular damage is proteinuria. Unlike haematuria, however, proteinuria is more commonly encountered in subjects with homozygous condition (haemoglobin SS) than in other haemoglobinopathies.
As to anatomic and pathologic findings in SCT, our patient's renal biopsy was typical [9]. Glomerular enlargement (Figures 1 and 2) and congestion is putatively related to compensatory hypersecretion of vasodilator prostaglandins in response to sickling. An additional factor contributing to renal hyperperfusion is increased nitric oxide synthesis in the glomeruli and distal nephron as described by Bank et al. [10]. Glomerular pathology, e.g. focal segmental glomerulosclerosis and membranoproliferative glomerulonephritis-like disease without immune complex deposits, however, are only seen in homozygotes and not in patients with SCT. Other prominent lesions (not demonstrable in our case) are in the medulla with interstitial fibrosis and tubular atrophy due to occlusion of blood flow in the vasa recta.
The treatment of sickle cell nephropathy is still at the centre of discussion. No specific therapy has been identified for the initial tubular changes, except for fluid balance. There is no evidence of the consistent benefit of non-steroidal anti-inflammatory drugs (in order to inhibit prostaglandin synthesis) or immunosuppressive drugs, such as steroids or cyclophosphamide [11]. Data on the effects of angiotensin-converting enzyme inhibitors or angiotensin-II receptor blockers on proteinuria and the progression of glomerular disease are still limited and need further evaluation [12].
In our case, dialysis was eventually paused 4 weeks after initial presentation. In a subsequent outpatient visit the patient's renal function was completely restored and treatment with darbepoetin alpha could be stopped.
Conflict of interest statement. None declared.
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References
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