Total protein, albumin, alpha1-microglobulin, and immunoglobulin G (IgG) were analyzed in 1,622 urine samples without Bence-Jones proteinuria or gross hematuria. There was correlation with the histological picture obtained on renal biopsy in 61 patients. We established 24-h reference intervals for alpha1-microglobulin and IgG on 659 urine samples with total protein and albumin excretion rates below 100 mg/24 h and 30 mg/24 h, respectively, and creatinine clearance above 80 ml/min. The central 95% reference interval was found to be between 4 and 17 mg/24 h for alpha1-microglobulin and between 3 and 8.5 mg/24 h for IgG. In 80 urine samples with albumin excretion rate above 30 mg/24 h and alpha1-microglobulin and IgG within their reference intervals, we analyzed the 95% central interval of the distribution of the IgG/albumin ratios, and it was found to be within 0.01 and 0.20 (0.90 confidence interval: 0.17-0.24). Proteinuria was considered to be of the selective glomerular type if the albumin excretion rate was abnormal and the IgG/albumin ratio was under 0.20, even when the IgG excretion was within a pathological range. For the classification of proteinuria as predominantly tubular, we estimated the alpha1-microglobulin/albumin ratio in 173 urine samples with normal excretion rates of albumin and IgG and pathological excretion of alpha1-microglobulin. The discriminating value of 0.91 (0.90 confidence interval: 0.78-1.08) was accepted in order to define proteinuria of a tubular origin in the presence of a pathological albumin excretion rate. The association between albumin and IgG excretion rates and tubular reabsorption of the alpha1-microglobulin normally filtered by the glomerulus was studied in 33 urine samples from patients with no histologically significant tubulo-interstitial or vascular disease and a serum creatinine concentration below 141 pmol/l. The optimal curve-fitting function between albumin plus IgG and alpha1-microglobulin excretion rates was of the quadratic type (r = 0.927). Mixed proteinuria was considered when both, albumin and alpha1-microglobulin excretion rates were pathological and could not be included in the previously described groups.

We studied the linearity and detection limits of the capillary zone electrophoresis system Capillarys in the measurement of serum monoclonal protein. Three monoclonal proteins with different isotypes and electrophoretic migrations were diluted with a hypo-gamma-globulinemic polyclonal serum pool. Mathematical linearity was observed for all monoclonal protein isotypes in the ranges studied without removing the polyclonal gamma-globulin background. Theoretical concentrations of 0.43, 0.89 and 0.33 g/L for monoclonal proteins immunoglobulin (Ig)G, IgA and IgM, respectively, gave a discernible spike by Capillarys, although they were measured as 0.76, 1.09 and 0.76g/L, respectively. We observed overestimation of monoclonal protein inversely correlated to concentrations below 15 g/L. All these limitations have to be taken into account when monitoring monoclonal proteins, because the loss of linearity and the protein background may hide an increase in concentration at low levels.

We conclude that the clinical laboratory should play an important role in the study of monoclonal gammopathies, since it is the only location where all M-protein patients are observed. On the other hand, studies of this type should be carried out over long-term periods, owing to the variations we have noted in the detection of M-proteins.

No method can accurately measure serum M-proteins over the entire concentration range. Estimation using polyclonal immunoglobulins and light chains represents a simple alternative to electrophoresis that is applicable to any serum M-protein concentration, regardless of electrophoretic migration and particularly for M-protein serum <20 g/L.

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