AN OUTBREAK OF NEPHROSIS

IN

MEMBRANOUS NEPHROPATHY

 CASE: 66 year-old woman

DIAGNOSIS: membranous nephropathy (MN confirmed by a renal biopsy at 1995)

table

* Alb(n): concentrations by nephelometry.   ** Alb(f): calculated by TP×electrophoretic albumin (%).

  f = 1.14n - 0.2, R = 0.99 (samle data 13)

CLINICAL COURSE

     This patient with membranous nephropathy (MN) had been suffered from nephrotic syndrome at 1995 ('95), and subsequently recovered by the treatment with high-dose prednisolone and immunosuppresseive agents.  After the recovery from the nephrotic syndrome , prednisolone and immunosuppressive agents were successfully  withdrawn for the following three years.  In the period of remission, her body weight was stable around 44 kg with no or slight edema of her lower extremities.  However, about 30 mg/dL of proteinuria persisted.

     At Oct. and Dec '98, her proteinuria was found to be increased at levels of 214 mg/dL and 299 mg/dL respectively.  She felt an increased general fatigue sensation at the same time.  At Jan. '99, she noticed newly developed edema in her abdominal wall.  Her body weight at Jan. '99 was 45 kg.  The proteinuria at a level of 612 mg/dL was found, and the relapse of nephrotic syndrome was considered.  The serum creatinine level at that time was 1.1 mg/dL.

        The three years' serial changes in electrophoretic serum albumin and alpha-2 globulin (×10; for ajusting the scale)  were shown in fig.2.  Although the albumin was gradually decreasing, other serologic markers were adequately preserved until Dec.'98 (table). 

       The serum electrophoretic pattern just at the relapse of nephrotic syndrome is shown in the riight of fig.1, in which an increased alpha-2 globulin fraction (arrow) is seen, in contrast to the essentially normal tracing of just before the relapse (left of fig 1).  

     At Jan. '99,  hyperlipidemia representing nephrosis was suddenly occured accompanying the increases in serum alpha-2 globulin, total cholesterol (T.Chol), and cholinesterase (ChE) concentrations.  In spite of the treatment with high-dose corticosteroid and intravenous supplemental albumin, her nephrotic syndrome has never been recovered (table).  

COMMENTS

     In the nephrotic syndrome, serum proteins of intermediate and middle size (40 - 200 kD) are lost into the urine resulting in a decrease in plasma (serum) albumin concentration and as a consequence a reduction in plasma colloid osmotic pressure (1).

     Hyperlipidemia, as well as hypoalbuminemia, is the most conspicuous serologic change of nephrotic syndrome.  The main cause(s) of the hyperlipidemia is considered to be increased hepatic protein synthesis, with  decreased clearance (or catabolism) and altered enzyme activities.  The signal for the lipoprotein hypersynthesis may mainly relate to decreased serum albumin concentration caused by urinary protein loss, and subsequent decreased osmotic pressure (2,3).   Although, the precise mechanism(s) of the development of hyperlipidemia is not yet clarified, in nephrosis the liver, in apparent compensatory response, increases synthesis of a group of these proteins, including macromolecular* proteins, defending plasma colloid osmotic pressure (2,4).    

     In this MN patient as seen in fig 2 and the table, after the slow deterioration in serum albumin concentration for about three years, in accordance with a "fall" of serum albumin concentration, a "leap" but not gradual change in the levels of serum alpha-2 globulin, total cholesterol and cholinesterase were occurred within a month.  From the observation of figure 2, it is suggested that the leap of alpha-2 globulin, main componets of which are alpha-2M globulin, haptoglobin and beta-lipoprotein,  may be based on "all-or-non" law.   

     These findings of this case suggest that the processes of liver protein synthesis must be suddenly switched over by some biological signals, including decreased and/or decreasing serum albumin (or other potent proteins) and subsequent decreased and/or decreasing plasma colloid osmotic pressure.  As a result, clinical nephrotic syndrome, in general, may suddenly outbreak in those patients with chronic kidney disease (CKD) like as MN.

(Nov.16, 08: INOUE T.MD)

* Molecular weight (MW): alpha-2M globulin 760 kD, Apo-B (LDL) 500 kD, ChE 350 kD.

 REFERENCES:

(1) Kang J, Holland M, Jones H, Kaysen GA. Coodinate augmentation in expression of genes encoding transcription factors and liver secretory proteins in hypo-oncotic states. Kidney Int 1999; 56:452-60.

(2) Appel GB, Valeri A, Appel AS, Blum CB. The hyperlipidemia of the nephrotic syndrome. Am J Med, 1989;87:45-50.

(3) Appel GB, Blum CB, Chien S, Kunis CL, Appel AS.  The hyperlipidemia of the nephrotic syndrome.  Relation to plasma albumin concentration, oncotic pressure, and viscosity. N Eng J Med 1985;312:1544-8.

(4) de Sain-van der Velden MG, Rabelink TJ, Reijngoud DJ, et al. Plasma alpha 2 macroglobulin is increased in nephrotic patients as a result of increased synthesis alone. Kidney Int 1998;54:530-5.

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