Myoglobinuric acute renal failure

Fig. 62. SDS-PAGE in normal controls and in patients with myoglobinuric acute renal failure, ALPE, or acute renal failure related to other etiologies. There were no bands which were specific to ALPE. ARF, acute renal failure (p. 68)...

Fig. 64. Proteomic analysis with a SELDI-TOF-MS. In single marker analysis left), the relative intensity of the 3.5 KDa peptide was high in the ALPE group. In the hierarchical clustering analysis with marker candidates, the heat map in the ALPE group differed from those in the myoglobinuric acute renal failure and normal groups (p. 69)...

In 1910, Meyer-Betz reported the first published case of acute renal failure with muscular pain, weakness, and dark urine after intense exercise [5]. In 1960, Howenstine reported that this type of acute renal failure was exercise-related myoglobinuria [6], However, at this time, it was impossible to distinguish hemoglobin from myoglobin, and this type of acute renal failure was considered to be a type of heat stroke. However, in 1970, Jackson [7] reported that this disorder was exercise-related renal failure and muscle damage, and this publication led to a gradual increase in research interest in myoglobinuric acute renal failure. In 1972, Hamilton et al. [8] and Knochel [9], respectively, reported that similar cases were exertional rhabdomyolysis. Matsumoto et al.[10] first reported this disorder in Japan in 1976. 

In 1982, we classified exercise-related acute renal failure into two types myoglobinuric acute renal failure, as had previously been reported, and non-myoglobin-related acute renal failure (exercise-induced acute renal failure). In 2002, the latter was named ALPE (Acute renal failure with severe Loin pain and Patchy renal ischemia after anaerobic Exercise) [4]. The term acute kidney injury (AKI) has recently been proposed as a patho-physiologically more correct alternative to the term acute renal failure. Therefore, exercise-induced acute renal failure in this book may be replaced by exercise-induced acute kidney injury. 

Massive rhabdomyolysis—myoglobinuric acute renal failure due to marathon, mountain climbing, etc. 

Minimum rhabdomyolysis—non-myoglobinuric acute renal failure due to exercise-induced acute renal failure—ALPE (acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise) after sprint, short track event such as 200-m race, etc. 

The other type is non-myoglobinuric acute renal failure, in which intense exercise over a short period of time, such as sprinting, causes minimal rhabdomyolysis without myoglobinuria, i.e., acute renal failure syndrome with severe loin pain and patchy renal vasoconstriction [2]. A recent study showed that anaerobic exercise caused this syndrome, and proposed that Acute renal failure with severe Loin pain and Patchy renal ischemia after anaerobic Exercise (ALPE) (exercise-induced acute renal failure) was a new type of acute renal failure syndrome [4]. 

Subsequently, we examined whether it is only patients with exercise-induced acute renal failure (ALPE) who show wedge-shaped contrast enhancement [15-18]. We performed delayed CT on a patient with ALPE and a patient with myoglobin uric acute renal failure (due to a malignant syndrome) when their serum creatinine levels were 3.0 and 1.5mg/dl, and compared the results. Wedge-shaped contrast enhancement was observed only in the patient with ALPE (Patient 19), and not in the patient with myoglobinuric acute renal failure. Diffuse contrast enhancement was noted (serum creatinine level, 3mg/dl) (Fig. 17). 

Fig. 17. Comparison of contrast enhancement 24h afterthe administration of contrast medium between exercise-induced acute renal failure (ALPE) and myoglobinuric acute renal failure (serum creatinine 3mg/dl). The patient with ALPE showed patchy wedge-shaped contrast enhancement, and the patient with myoglobinuric acute renal failure showed diffuse contrast enhancement...

Mild rhabdomyolysis (which differs from that in myoglobinuric acute renal failure patients), and serum levels of creatine phosphokinase (CPK) and myoglobin, which are normal or slightly increased (less than 7 times the reference value for serum myoglobin, and less than 9 times the reference value for CPK). 

Some patients have nontypical ALPE. Some do not clearly remember having exercised [1,28,29], and others do not complain of loin pain [30,31]. In addition, others concurrently develop myoglobinuric acute renal failure and exercise-induced acute renal failure (ALPE), and show the characteristics of both disorders [32,33],... 

In order to clarify the vasoconstrictive factors, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was carried out in the initial phase of our study. In the patients with myoglobinuric acute renal failure, myoglobin bands were detected. However, there were no ALPE-specific bands (Fig. 62). 

Fig. 63. Single marker analysis with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) in the ALPE, myoglobinuric acute renal failure, and normal groups. In the ALPE group, the relative intensity of a 3.5 KDa/4.3 KDa peptide was higher than that in the other groups...

Differentiation of ALPE from Myoglobinuric Acute Renal Failure... 

We compared ALPE (non-myoglobinuric acute renal failure) with myoglobinuric acute renal failure (Table 11). 

Exercise-induced acute renal failure (ALPE) Myoglobinuric acute renal failure... 

Myoglobinuric acute renal failure developed after continued strenuous exercise. Marked muscular destruction (rhabdomyolysis) resulted in dark urine. However, there was no pain, and dehydration was marked. The CPK level showed a 10- to 20-fold increase compared with the reference value. Delayed CT showed diffuse contrast enhancement (Fig. 74). 

In the patients with ALPE, bone scans showed no muscular uptake of methylene diphosphonate (MDP). However, upper/lower limb muscle uptake of MDP was found in the patients with myoglobinuric acute renal failure (Fig. 75). 

As shown in Fig. 76, exercise-related acute renal failure is classified into two types myoglobinuric acute renal failure and non-myoglobinuric acute renal failure. The latter is represented by ALPE. The grade of rhabdomyolysis and the type/grade of muscle fibers affected are shown in Fig. 76. Pathogenetic factors for ALPE should be investigated in the future. 

ALPE MDP bone scan Myoglobinuric acute renal failure MDP bone scan... 

Fig. 75. Bone scan with MDP. In a patient with ALPE (left), there was no muscular uptake of MDP. However, muscular accumulation of MDP (arrows) was observed in a patient with myoglobinuric acute renal failure (right). In the ALPE patient, it was impossible to evaluate the presence or absence of patchy accumulation in the kidney...

Fig. 76. Comparison of the pathogenesis between myoglobinuric acute renal failure and non myoglobinuric acute renal failure represented by ALPE (hypothesis)...

ALPE is different from exertional rhabdomyolysis (myoglobinuric acute renal failure). 

Rice EK, Isbel NM, Becker GJ, Atkins RC, McMahon LP. Heroin overdose and myoglobinuric acute renal failure. Clin Nephrol 2000 54(6) 449-54. 

Zager RA. Studies of mechanisms and protective maneuvers in myoglobinuric acute renal failure. Lab Invest 1989 60 619-629. 

Patel R, Ansari A, Hughes JL. Myoglobinuric acute renal failure associated with phencyclidine abuse. West J Med 1979 131 244-247. 

Patel R, Das M, Patazzolo M, Ansari A, Balasubramaniam J. Myoglobinuric acute renal failure in phencyclidine overdose. Report of observations in eight cases. Ann Emerg Med 1980 9 549-553. 

Metabolic acidosis with an increased SAG commonly results from increased endogenous organic acid production. In lactic acidosis, lactic acid accumulates as a by-product of anaerobic metabolism. Accumulation of the ketoacids /S-hydroxybutyric acid and acetoacetic acid defines the ketoacidosis of uncontrolled diabetes mellitus, alcohol intoxication, and starvation (see Table 51-5). In advanced renal failure, ac-cumulation of phosphate, sulfate, and organic anions is responsible for the increased SAG, which is usually less than 24 mEq/L." The severe metabolic acidosis seen in myoglobinuric acute renal failure caused by rhabdomyolysis may be caused by the metabolism of large amounts of sulfur-containing amino acids released from myoglobin. 

Bidani AK, Churchill PC, Packer W. Theophylline-induced protection in myoglobinuric acute renal failure Further chracterization. 

Alejandro DSJ, Petersen J Myoglobinuric acute renal failure in a cardiac transplant patient taking lovastatin and cyclospccine J Am Soc Nephrol (1994) 5,153-160... 

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