Original Papers €> 1990 S. K arger A ü . Basel 0028 2 7 66/90/0554-0361$2.75/0
Nephron 1990;55:361-367
Renal Elimination of Beta-2-Microglobulin and Myoglobin in Patients with Normal and Impaired Renal Function J. Floegea , M.F. Wilks ', M. Soose a , J. Kotzerkeb, S. Shaldon c , K.M. Koch" ' Departments of “Nephrology and '’Nuclear Medicine, Medizinische Hochschule Hannover, FRG; c Department of Nephrology, University Hospital Nimes, France
Key Words. p2-Microglobulin • Low-molecular-weight proteins • Myoglobin
Introduction Recently p2-microglobulin has received increased in terest among nephrologists due to its association with dialysis-related amyloidosis [1, 2]. The pathogenesis of dialysis-related amyloidosis has not been clarified yet, but it is generally accepted that the marked retention of p2-microglobulm in uremia is a prerequisite for the devel opment of this new type of amyloidosis. The retention of p2-microglobulin in end-stage renal failure is based on the fact that normally more than 95% of this low-molecu lar-weight (11.8 kD) protein is excreted via the kidney [3]. In accordance with this is the finding of a logarithmic correlation of the plasma p2-microglobulin concentration 1 The authors thank C. Olbricht, Medizinische Hochschule Han nover, for helpful discussions during the preparation of the manu script.
with the inulin clearance [4], p2-Microglobulin is freely filtered in the glomerulus [5, 6]. Like other low-molecu lar-weight proteins, p2-microglobulin is then almost com pletely reabsorbed by proximal tubular epithelium and eventually hydrolyzed within the cells to its constituent amino acids [7], In 1972 Ravnskov et al. [8] proposed on the basis of renal arteriovenous extraction measurements in humans that in addition to glomerular filtration and tubular proteolysis of p2-microglobulin a peritubular mode of removal may also participate in the renal elimi nation of this protein. This proposal was derived from the findings that the renal arteriovenous extraction of p2-microglobulin was higher than that of inulin in some pa tients and that the extraction of p2-microglobulin, but not that of inulin, decreased in renal insufficiency. In this study we, therefore, attempted to further investigate this issue by examining the renal elimination of polyfructo-
Downloaded by: Kings's College London 137.73.144.138 - 11/3/2017 8:23:23 AM
Abstract. Since the demonstration that p2-microglobulin ((LM) is an amyloidogenic protein in man, the excretion of this low-molecular-weight protein under conditions with normal and reduced renal function has received increased interest. The renal arteriovenous extraction of p2M, polyfructosan (an inulin analogue), and a second low-molecularweight protein, myoglobin, was measured in vivo in 16 human kidneys with normal renal function/gross morphology and in 22 kidneys with reduced function. In kidneys with normal function, the extraction of p2M significantly exceeded that of polyfructosan (0.198 ± 0.037 vs. 0.182 ± 0.05; p = 0.04), while that of myoglobin (0.177 ± 0.068) was not different from that of polyfructosan. In kidneys with reduced function, the extraction of polyfructosan or myoglobin was not significantly altered. In contrast, the p2M extraction decreased to 0.110±0.060 (p
Nephron 1990;55:361-367
Renal Elimination of Beta-2-Microglobulin and Myoglobin in Patients with Normal and Impaired Renal Function J. Floegea , M.F. Wilks ', M. Soose a , J. Kotzerkeb, S. Shaldon c , K.M. Koch" ' Departments of “Nephrology and '’Nuclear Medicine, Medizinische Hochschule Hannover, FRG; c Department of Nephrology, University Hospital Nimes, France
Key Words. p2-Microglobulin • Low-molecular-weight proteins • Myoglobin
Introduction Recently p2-microglobulin has received increased in terest among nephrologists due to its association with dialysis-related amyloidosis [1, 2]. The pathogenesis of dialysis-related amyloidosis has not been clarified yet, but it is generally accepted that the marked retention of p2-microglobulm in uremia is a prerequisite for the devel opment of this new type of amyloidosis. The retention of p2-microglobulin in end-stage renal failure is based on the fact that normally more than 95% of this low-molecu lar-weight (11.8 kD) protein is excreted via the kidney [3]. In accordance with this is the finding of a logarithmic correlation of the plasma p2-microglobulin concentration 1 The authors thank C. Olbricht, Medizinische Hochschule Han nover, for helpful discussions during the preparation of the manu script.
with the inulin clearance [4], p2-Microglobulin is freely filtered in the glomerulus [5, 6]. Like other low-molecu lar-weight proteins, p2-microglobulin is then almost com pletely reabsorbed by proximal tubular epithelium and eventually hydrolyzed within the cells to its constituent amino acids [7], In 1972 Ravnskov et al. [8] proposed on the basis of renal arteriovenous extraction measurements in humans that in addition to glomerular filtration and tubular proteolysis of p2-microglobulin a peritubular mode of removal may also participate in the renal elimi nation of this protein. This proposal was derived from the findings that the renal arteriovenous extraction of p2-microglobulin was higher than that of inulin in some pa tients and that the extraction of p2-microglobulin, but not that of inulin, decreased in renal insufficiency. In this study we, therefore, attempted to further investigate this issue by examining the renal elimination of polyfructo-
Downloaded by: Kings's College London 137.73.144.138 - 11/3/2017 8:23:23 AM
Abstract. Since the demonstration that p2-microglobulin ((LM) is an amyloidogenic protein in man, the excretion of this low-molecular-weight protein under conditions with normal and reduced renal function has received increased interest. The renal arteriovenous extraction of p2M, polyfructosan (an inulin analogue), and a second low-molecularweight protein, myoglobin, was measured in vivo in 16 human kidneys with normal renal function/gross morphology and in 22 kidneys with reduced function. In kidneys with normal function, the extraction of p2M significantly exceeded that of polyfructosan (0.198 ± 0.037 vs. 0.182 ± 0.05; p = 0.04), while that of myoglobin (0.177 ± 0.068) was not different from that of polyfructosan. In kidneys with reduced function, the extraction of polyfructosan or myoglobin was not significantly altered. In contrast, the p2M extraction decreased to 0.110±0.060 (p
