The American Journal of the Medical Sciences. 258(6):386-393, December 1969.
Abstract:
colon; Twenty-nine patients with persistent proteinuria (urinary protein content more than 2 g per day) underwent renal biopsies and determinations of the selectivity index. The selectivity index showed only fair correlation with the patient's response to treatment and did not permit an accurate prediction of the histologic appearance of the glomerulus. This lack of correlation of the selectivity index with the glomerular pathology is at variance with most of the findings previously reported.
29人の1日2g以上の蛋白尿患者に腎生検と蛋白の選択性をみた。
蛋白選択性は、ステロイドの反応性とのみ正の相関を示したが、
腎生検の組織像とは相関がなかった。
Fractional excretion of high- and low-molecular weight proteins and outcome in primary focal segmental glomerulosclerosis.
Clin.Nephrol 2007 Oct;68(4):201-8.
AIMS: Predicting prognosis in patients with a nephrotic syndrome due to primary FSGS remains difficult. Recently, it was suggested that the fractional excretion (FE) of IgG (threshold 0.14%) predicts remission, progression to renal failure and response to therapy in FSGS. In the present study, we evaluated the usefulness of FE IgG to guide treatment of patients with primary FSGS in clinical practice. METHODS: From 1995 onward, FE of IgG was measured in 32 adult patients with biopsy-proven primary FSGS. In addition, we quantified 24-hour proteinuria, selectivity index (SI) and FE of albumin, IgG, transferrin and beta2-microglobulin (beta2m). We evaluated outcome in patients with FE IgG above and below 0.14%. Receiver-operating curves were used to determine the best cut-off values for other urinary proteins in predicting remission, response to therapy and renal survival. RESULTS: Mean age was 45 +/- 17 years, serum creatinine 128 +/- 58 micromol/l, proteinuria 10.3 +/- 4.7 g/day and serum albumin 18 +/- 7 g/l. Twenty-three patients received immunosuppressive therapy (9 prednisone and 14 prednisone and cyclophosphamide). After a median follow-up of 58.3 (4.9-127.6) months, 17 patients were in remission (10 complete, 7 partial), 6 patients still had a nephrotic syndrome, renal failure developed in 6 patients, and 3 patients had died. Remission rate was similar in patients with FE IgG less or greater than 0.14%. More patients with FE IgG > 0.14% had received immunosuppressive therapy. Additional analysis revealed that the predictive value of FE of albumin, transferrin and beta2m was low. In untreated patients, FE beta2m < 1% predicted a better renal survival. CONCLUSIONS: Our data indicate that a FE IgG > 0.14% is not invariably associated with a poor outcome in patients with primary FSGS. Therefore, high FE IgG should not lead to therapeutic nihilism. Low FE beta2m predicted a good prognosis without immunosuppressive therapy.
蛋白のFractional Excretion（FE)がFSGSの予後と相関するか
IgGのFEがFSGSの予後と相関するかみるために、32人のFSGS患者を集め、
IgG、アルブミン、トランスフェリン、β2-MGのFE、と24時間尿蛋白、蛋白選択性をみた。
年齢は45プラスマイナス17歳、血清Cr 128±58μmol/l、尿蛋白 10.3±4.7g/日、
フォローの中央値は58.3カ月（約6年）
32人中、9人がPSL、14人がPSL+CYCを受けた。
17人が寛解、(10人がCR、7人がPR）、6人がネフローゼのまま、6人が腎不全となり、3人が死亡。
FEIｇGは、FSGSの寛解の予測には役立たなかった。
未治療の患者ではFEβ2-MGが1.0％未満が、腎生存を予測因子だった。
Paediatr. padol1980;15(2):131-6.
The prognosis of idiopathic nephrotic syndrome: a comparative study between the index of selectivity of proteinuria and the findings in renal biopsies.
In 20 children with idiopathic nephrotic syndrome, the morphological changes in the glomeruli were compared with the index of selectivity of proteinuria. For the determination of the index of selectivity, the clearances of IgG and transferrin were used. A high correlation was found between the morphological changes and the index values. An index of selectivity of proteinuria of 0.20 proved to be the critical value for differentiating between a steroid sensitive and a steroid resistant INS.
20人のネフローゼの小児。
形態学的変化と蛋白選択性には相関を認めた。
また選択性が0.20できると、ステロイド感受性と抵抗性を分けられた。
1980 Dec;13(4):376-85.
Simultaneous studies of serum and urinary proteins for evaluation and diagnosis of glomerular damages in proteinuric patients.
Simultaneous studies of serum and urinary proteins in 294 adult proteinuric patients are presented. Our data showed that these studies can provide valuable guides for clinical diagnosis. In the group of idiopathic nephrotic syndrome, hypoalbuminemia, hypogammaglobulinemia and hyper-alpha 2 globulinemia were most marked. Urinary protein electrophoresis (PEP) showed a well-selective pattern with albumin and beta globulin as the main constituents. In the other groups of proteinuric patients the hypoalbuminemia and hyper-alpha 2 globulinemia were milder and urinary PEP generally showed non-selective pattern. In the groups of acute glomerulonephritis and lupus nephropathy, C3 was generally decreased; polyclonal gammopathy was frequently encountered and alpha 1 acid glycoprotein was markedly increased. In the cases of chronic glomerulonephritis and diabetic nephropathy and the levels of gamma globulin, C3 and alpha 2 acid glycoprotein were usually within normal limits. Urinary protein selectivity index in this series of adult patients was not a useful diagnostic parameter.
尿蛋白陽性患者での血清や尿の蛋白の評価と糸球体障害の診断の関係
294人の成人、尿蛋白陽性者。
尿蛋白の選択性は診断に役立つパラメーターではなかった。
Nephron 1986;42(3):236-9.
Protein selectivity in IgA nephropathy.
The protein selectivity index was measured in 68 patients (53 males, 15 females) with proteinuria due to IgA nephropathy to determine whether it bore any relationship to other clinical and pathological features of known prognostic significance. The mean age of the patients was 25 +/- 8 years with a follow-up period of 42 +/- 35 months. Forty-six presented with asymptomatic haematuria and proteinuria, 17 with macroscopic haematuria and 5 with the nephrotic syndrome. Twenty-three (34%) patients had selective proteinuria and 45 (66%) had non-selective proteinuria. Patients with non-selective proteinuria had more glomerulosclerosis (29% +/- 20 vs. 16% +/- 20, p less than 0.02), higher serum creatinine (1.47 mg/dl +/- 0.70 vs. 1.17 mg/dl +/- 0.33, p less than 0.02), lower creatinine clearance (79 ml/min +/- 28 vs. 95 ml/min +/- 25, p less than 0.02), and higher incidence of hypertension (chi 2 = 3.84, p less than 0.05) when compared to those with selective proteinuria. The protein selectivity was measured at the end of the study. Of the 5 patients with the nephrotic syndrome, 1 had poorly selective proteinuria and failed to remit and 4 had highly selective proteinuria who either remitted spontaneously (1 patient) or with treatment (3 patients). The results suggest that patients with IgA nephropathy and poorly selective proteinuria are more likely to have other features indicating a poor prognosis such as glomerulosclerosis, renal impairment and hypertension.
68人のIgA腎症
46人が無症候性の血尿、蛋白尿、17人が肉眼的血尿、5人がネフローゼ。
23人（34％）が高選択性、45人（66％）が非選択性
高選択性患者では、糸球体硬化、腎障害、高血圧が軽かった。
5人のネフローゼ中、1人が非選択性で、寛解にならず、
4人は高選択性で、1人は自然経過で、3人は治療で寛解になった。
J Lab Clin Med 1997 Jan;129(1):47-52.
Comparison of noninvasive methods for distinguishing steroid-sensitive nephrotic syndrome from focal glomerulosclerosis.
Although renal biopsy is the definitive investigation in kidney disorders and is particularly helpful in distinguishing steroid-responsive nephrotic syndrome (SRNS) from focal glomerulosclerosis (FGS), it is attended by a small risk to the patient. Accordingly, noninvasive tests have been used to predict the response to steroids and the underlying renal histologic diagnosis in nephrotic syndrome. The performance of these tests has, however, not been encouraging. We have therefore compared the reliability of the conventional selectivity index (SI) of serum and urinary transferrin and immunoglobulin G (IgG) against other tests of urinary proteins, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE), and isoelectric focusing (IEF). SI, SDS PAGE, and IEF were carried out in children with nephrotic syndrome within 2 months of clinical presentation. Thirty-one children who had SRNS were compared with 26 who had biopsy-proved FGS and who were steroid resistant. SDS PAGE and IEF revealed excretion of albumin and transferrin only, with homogeneous anionic charge, respectively, in SRNS but unrestricted excretion of additional proteins IgG, beta2-microglobulin, and lysozyme with heterogeneity of electrical charge in FGS. With SDS PAGE and IEF we were able to predict all children who had SRNS and FGS; the SI test predicted all steroid-resistant patients with FGS but was able to predict only 41.7% of the patients with SRNS. Therefore the negative predictive value for steroid response was 58.8% by SI and 100% by SDS PAGE and IEF; the positive predictive value was 100% by SI, SDS PAGE, and IEF. We illustrate the value of SDS PAGE in guiding management in a further seven children with FGS in whom there was either an initial discordance between renal biopsy results and steroid responsiveness or when biopsy was delayed. Accordingly, SDS PAGE and IEF of urinary proteins appear to be useful tests in the diagnosis and management of SRNS and FGS.
31人のステロイド感受性ネフローゼと、ステロイド抵抗性で、腎生検でFSGSと診断された26人を比較。
SDS-PAGE,Isoelectric focusing(IEF)とSIを比較。
SDS-PAGEとIEFでは、SRNSとFSGSを分けられた。
SIは、FSGSを100％識別したが、SRNSでは41.7％のみの感度だった。
ステロイド抵抗性に対する陰性尤度比はSDS-PAGEとIEFで100％、SIで58.8％、
陽性尤度比はSDS-PAGE、IEF、SI全てで100％だった。
Kidney Int. 2000 Oct;58(4):1732-41.
A modern approach to selectivity of proteinuria and tubulointerstitial damage in nephrotic syndrome.
BACKGROUND: The selectivity of proteinuria, introduced in clinical nephrology in 1960 and useful in predicting steroid responsiveness in nephrotic syndrome, found little place in clinical practice in subsequent decades, since its assessment did not appear to help predict histologic diagnosis or determine prognosis. The amount of proteinuria and the degree of tubulointerstitial damage appeared to be better predictors of functional outcome. A correlation between them has been found, referred to some toxicity of proteinuria on tubular cells, but so far no single feature or component of proteinuria has been identified as being responsible for this toxicity. METHODS: We evaluated 89 patients with nephrotic syndrome [9 with minimal change disease (MCD), 29 with primary focal segmental glomerulosclerosis (FSGS), and 51 with idiopathic membranous glomerulonephritis (MGN)] to determine if the selectivity of proteinuria was associated with tubulointerstitial damage. A semiquantitative grading of histologic lesions and qualitative evaluation of the "tubular" component of proteinuria expressed as a pattern of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and as fractional excretion of the low molecular weight (LMW) protein alpha1-microglobulin (FE alpha1m) were used. A second aim of the study was to assess the predictive value on functional outcome [remission or progression to chronic renal failure (CRF)] and response to therapy of the selectivity of proteinuria, considered alone and in combination with FE alpha1m. RESULTS: Proteinuria was classified as highly selective [selectivity index (SI) < or = 0.10, N = 15], moderately selective (SI > or = 0.11 < or = 0.20, N = 34), or nonselective (SI > or = 0.21, N = 40). A significant relationship was found between the SI and the histologic degree of tubulointerstitial damage (score 0 to 1 vs. score > or =2, P = 0.000), severity of the tubular component of proteinuria (mixed SDS-PAGE pattern with LMW proteins not lower than 23 kD vs. mixed pattern with LMW proteins up to 20 to 10 kD, P = 0.000), and FE alpha1m (values below vs. above a defined cut-off, P = 0.000). The functional outcome was evaluated in 60 patients with baseline normal renal function (serum creatinine 0.97 +/- 0.19 mg/dL). The patients with high, moderate, or nonselective proteinuria had 100, 50, and 29% of complete or partial remission (P = 0.0001) and 0, 25, and 35% of progression to CRF, respectively (P = 0.050). In 45 patients with moderately selective (N = 28) and nonselective (N = 17) proteinuria, according to some arbitrary cutoffs for FE alpha1m (MGN, < or = vs. > 0. 240% of creatinine clearance; FSGS and MCD, < or = vs. > 0.350%), the remission rate was 62 versus 6% in patients with FE alpha1m below or above the cutoffs (P = 0.0001), and progression to CRF was 7 and 69%, respectively (P = 0.0001). The response to therapy (complete or partial remission at the last observation), evaluated retrospectively in 40 patients, was 100, 67, and 33% in high, moderate, and nonselective proteinuria (P = 0.0002); in 30 patients with moderate and nonselective proteinuria, according to an FE alpha1m value that was < or = or > the cutoffs, the response rate was 75 versus 10% (P = 0.001). CONCLUSIONS: There is a significant relationship between selectivity of proteinuria and tubulointerstitial damage. Moreover, the selectivity of proteinuria has a predictive value on functional outcome. When proteinuria is highly selective, the tubulointerstitial damage is rather infrequent, and 100% of patients develop clinical remission. When proteinuria is moderately selective or nonselective, increasing numbers of patients develop tubulointerstitial damage; in these patients, the functional outcome and response to therapy is partly dependent on tubulointerstitial involvement, and the best predictor of functional outcome is the combination of SI and FE alpha1m.