J Am Soc Nephrol 12: S44 S47, 2001

New Aspects of the Treatment of Nephrotic Syndrome

ANKE SCHWARZ
Department of Nephrology, Medizinische Hochschule Hannover, Hanover, Germany.

Abstract. The nephrotic syndrome, caused by glomerulonephritis, diabetes mellitus, or amyloidosis, is still a therapeutic
challenge. Newer therapeutic approaches may be sought in the
fields of immunosuppression, nonspecific supportive measures, heparinoid administration, and removal of a supposed
glomerular basement membrane toxic factor. In immunosuppression, the newer drugs now used in organ transplantation
(cyclosporine, tacrolimus, and mycophenolate mofetil) can
also be used in the treatment of glomerulonephritis. In nonspecific supportive treatment, angiotensin II receptor antagonists
are now used in addition to angiotensin-converting enzyme
inhibitors. Positive effects of hydroxymethylglutaryl coenzyme
A reductase inhibitors on the nephrotic syndrome have not yet
been proven. Cyclooxygenase II inhibitors must be tested but

probably have too many renal side effects, similar to those of

nonsteroidal anti-inflammatory drugs. Heparinoids or glycosaminoglycans serve as polyanions and thus have protective
effects on the negative charge of the glomerular basement
membrane. They can now be administered as oral medications.
The removal of a supposed glomerular basement membrane
toxic factor that induces proteinuria has been attempted for 20
yr and now is usually performed using immunoadsorption.
Especially in cases of recurrent nephrotic syndrome after renal
transplantation for patients with glomerulonephritis, this approach has been successful in decreasing proteinuria, although
in most cases its effect is not lasting but must be continuously
renewed.

The nephrotic syndrome with heavy proteinuria is the most

severe disease encountered in nephrology, whether the cause is
glomerulonephritis, diabetes mellitus, or amyloidosis. In severe cases, patients are grateful when they have reached endstage renal disease, which usually means the cessation of
kidney function and an end to their loss of protein. In some
cases, this cannot be achieved with any methods other than
renal ablation, e.g., embolization of the kidneys.
The protein barrier of the glomerular basement membrane is
charge-selective for smaller proteins and size-selective for
larger proteins (13). The first stage of fluid accumulation
before hypoproteinemia is sodium retention by the distal tubules, perhaps mediated by an abnormal response to atrial
natriuretic hormone (4,5). The consequences of severe proteinuria are excessive tubular reabsorption of protein, disturbances
of intracellular tubular signaling (with release of vasoactive
and inflammatory substances into the interstitium), interstitial
inflammatory reactions, and finally renal insufficiency (6).
Many attempts have been made to reverse or influence
protein passage through the glomerular basement membrane,
especially in cases in which causal therapy of the underlying
disease has proved impossible, such as some cases of glomerulonephritis and cases of diabetes mellitus or amyloidosis.
New aspects of the treatment of the nephrotic syndrome represent the subject of this article.

Immunosuppressive Drugs

Correspondence to Dr. Anke Schwarz, Department of Nephrology, Medizinische

Hochschule Hannover, Carl-Neuberg Strasse 1, D-30629 Hanover, Germany.
Phone: 511-5326319; Fax: 511-552366; E-mail: schwarz.anke@mh-hannover.de
1046-6673/1202-0044
Journal of the American Society of Nephrology
Copyright 2001 by the American Society of Nephrology

The first controlled trial of immunosuppressive treatment in

adult patients with glomerulonephritis and the nephrotic syndrome was undertaken in 1970 with prednisone. That trial
confirmed that some kinds of glomerulonephritis responded to
immunosuppressive therapy better than others and that patients
with the reversal of proteinuria usually did not develop renal
insufficiency (7). Consequently, other immunosuppressive
drugs, such as azathioprine, cyclophosphamide, and chlorambucil, were tested for the treatment of glomerulonephritis; they
improved and stabilized the outcome of treatment, especially
for the poorly responding forms of glomerulonephritis [such as
focal segmental glomerular sclerosis (FSGS) and membranous
glomerulonephritis] (8 10). In recent years, immunosuppressive drugs used for organ transplantation have been increasingly tested for the treatment of resistant cases of
glomerulonephritis.
Cyclosporine acts by inhibiting interleukin-2 production and
has been used in transplantation since 1980. It has been tested
in the treatment of glomerulonephritis since 1986 (11). However, only in 1999 was a controlled trial performed with
patients with steroid-resistant FSGS (n 49); that trial demonstrated that significantly more patients treated with cyclosporine experienced partial or complete remission, compared
with patients not treated (12). Controlled trials are difficult to
perform for membranous nephropathy, because of the variable
spontaneous course of the disease (13). However, a significant
reduction in proteinuria was observed for cyclosporine-treated
patients with membranous nephropathy (14,15). The mechanism of action of cyclosporine in the treatment of glomerulonephritis is not known. Side effects of treatment are hypertension and nephropathy (16).
Tacrolimus also blocks the activation of the interleukin-2

J Am Soc Nephrol 12: S44 S47, 2001

gene in T cells. It has been used in transplantation since 1990

and has also been used for the treatment of glomerulonephritis
in some treatment-resistant cases (17). No controlled studies
exist. As for cyclosporine, the mechanism of action on proteinuria is not known. However, in one case of membranoproliferative glomerulonephritis that was treated successfully with
cyclosporine, a treatment switch to tacrolimus (performed because of cyclosporine side effects) caused a relapse of proteinuria, whereas cyclosporine subsequently reinduced remission
(18). Therefore, there must be a difference in the actions of
these two drugs.
Mycophenolate mofetil has been used in transplantation
since 1993 (19). It suppresses de novo purine synthesis, thus
inhibiting T and B cell proliferation as well as the proliferation
of smooth muscle cells and fibroblasts; perhaps it is through
this mechanism that the drug protects the kidney from progressive disease. Mycophenolate mofetil is used in the treatment of
glomerulonephritis in resistant cases such as cases of IgA
nephropathy (20). No controlled studies have been performed.
The cases presented in the literature primarily involved patients
who had been heavily pretreated with other drugs, but those
findings indicated at least partial remission in 47 of 63 cases
(75%) (20 26).

Nonspecific Supportive Treatment

Angiotensin-converting enzyme (ACE) inhibitors are known
to decrease proteinuria by reducing GFR and thus influencing
mesangial processes as well as the sieving coefficient and size
selectivity of the glomerular basement membrane (27,28). Angiotensin II receptor antagonists have the same effects on
proteinuria and are as effective as ACE inhibitors (28,29). The
possibility of additive effects of the two types of compounds
has not yet been tested.
Hydroxymethylglutaryl coenzyme A reductase inhibitors
have strong lipid-lowering effects. It has been suggested that
dyslipoproteinemia caused by renal disease, and especially by
the nephrotic syndrome, may contribute not only to the accelerated development of atherosclerosis but also to the progression of renal disease (30). In addition to their lipid-lowering
effects, statins improve endothelial function and alter the local
fibrinolytic balance within the vessel wall, in a way that tends
to increase fibrinolytic activity (31,32). However, the lipidlowering effects of hydroxymethylglutaryl coenzyme A reductase inhibitors with respect to the extent of proteinuria in cases
of nephrotic syndrome have not been proven (33).
Nonsteroidal anti-inflammatory drugs have been shown to
reduce proteinuria by reducing the GFR (34). The multiple
renal side effects caused by prostaglandin inhibition, such as
hemodynamic effects on renal perfusion, edema formation,
hyperkalemia, and renal toxicity, have led to the restricted use
of these drugs. Selective cyclooxygenase II inhibitors have
been shown to have the same beneficial effects on proteinuria
in rats, with fewer side effects, when administered in low
doses; at high doses, cyclooxygenase II selectivity is lost and
more of the typical aforementioned side effects of nonsteroidal
anti-inflammatory drugs may be observed (35). However, no
studies have been performed with human subjects.

Nephrotic Syndrome

S45

Heparinoids
Heparin treatment in glomerulonephritis was shown to lower
proteinuria and ameliorate renal insufficiency, in the short and
long term, as early as 30 yr ago; these findings were ascribed
to the anticoagulant effect of heparin (36,37). However, in an
experimental study using rats, it was shown that glycosaminoglycans, which are part of the glomerular basement membrane
as well as of heparin, act as polyanions and antagonize the
damaging effects of polycations such as protamine, reestablishing the negative charge of the glomerular basement membrane and the podocyte architecture (38). In addition, mesangial cell turnover is decreased (39 41). Especially in cases of
diabetes mellitus characterized by disturbances of extracellular
matrix degradation, glycosaminoglycans modulate the consequences of these defects on the glomeruli and the retina by
inhibiting the overactive transforming growth factor- cascade
(42). When sulfated glycosaminoglycans were administered to
human subjects for 1 mo, the effect on proteinuria was small
but statistically significant (43).
Glycosaminoglycans are now available as nonanticoagulant
oral medications. Pentosan polysulfate is a sulfated oligosaccharide of plant origin with some of the nonanticoagulant
features of unfractionated heparin (40). Controlled long-term
studies with nephrotic patients with glomerulonephritis or diabetes mellitus are awaited. To date, it has seemed justified to
treat severely nephrotic patients with low-mol wt heparin instead of phenprocoumon to establish anticoagulation (which is
necessary for these patients, in their hypercoagulable state), as
well as to achieve possible beneficial effects on proteinuria.

Removal of a Glomerular Basement Membrane

Toxic Factor
The discussion regarding a proteinuric factor in glomerulonephritis, and especially in FSGS, has been underway since the
observation of the early recurrence of heavy proteinuria after
renal transplantation in a patient with FSGS (44). This suspicion was confirmed by the report of fetal transmission of
proteinuria to two children of a mother with heavy proteinuria
attributable to FSGS (45). The reduction of posttransplantation
proteinuria attributable to recurrent mesangioproliferative glomerulonephritis by plasma exchange was first reported by
Solomon et al. (46). The fact that immunoadsorption was more
effective than plasma exchange (83% versus 64% mean reduction of proteinuria) in cases involving nephrotic syndrome
attributable to glomerulonephritis was reported by Dantal et al.
(47,48). Some patients experience complete or partial remission of the nephrotic syndrome after a certain period of plasma
removal, but most patients experience relapse 3 to 10 d after
the cessation of therapy. Chronic intermittent immunoadsorption must be considered for these patients and seems to be
possible for at least months (J. Dantal, personal communication, June 2000). Interestingly, low-density lipid apheresis is
also able to decrease proteinuria, in a manner similar to that of
immunoadsorption (49,50). Whether this method could be successfully used for patients with nephrotic syndrome attributable to causes other than glomerulonephritis, e.g., diabetes
mellitus or amyloidosis, remains to be investigated (51).

S46

Journal of the American Society of Nephrology

It is not yet possible to identify the proteinuric factor.

Koyama et al. (52) obtained T cell hybridomas from T cells
from a patient with minimal-change nephropathy, which produced a glomerular permeability factor that induced proteinuria
and partial fusion of glomerular epithelial cells in rats. Those
authors speculated that the factor was a lymphokine. Savin et
al. (53) identified such a circulating factor in patients with
recurrent nephrotic syndrome after renal transplantation. In
rats, this factor was assumed to be tumor necrosis factor-
(54).

Conclusions
For patients with nephrotic syndrome attributable to treatment-resistant glomerulonephritis, some benefits may be obtained with the new immunosuppressive drugs used in organ
transplantation, such as cyclosporine, mycophenolate mofetil,
and in some cases tacrolimus. For patients with diabetes mellitus or amyloidosis and for some patients with glomerulonephritis that does not respond to any immunosuppressive treatment, no causal treatment is currently possible. As a
nonspecific supportive treatment, angiotensin II receptor antagonists are as efficacious as ACE inhibitors. The anticoagulation treatment required for the nephrotic syndrome should
perhaps be performed with low-mol wt heparin instead of
phencoumaron, because of the superior antiproteinuric effects
and protective effects on the glomerular basement membrane
exhibited by heparin. Alternatively, in addition to their other
medications, these patients should receive the oral nonanticoagulant heparan sulfate. For patients with treatment-resistant
FSGS in native kidneys or in renal transplants or for patients
with severe nephrotic syndrome attributable to other glomerulonephritides, the removal of a proteinuric factor, via plasmapheresis or immunoadsorption, could be attempted. If this
removal is effective but does not lead to persistent remission,
chronic intermittent immunoadsorption should be considered.
Even today, renal ablation (by embolization or surgical removal of the kidneys) and subsequent chronic dialysis treatment may be the only feasible way to protect patients from the
consequences of severe proteinuria (55,56).

References
1. Shemesh O, Ross JC, Deen WM, Grant GW, Myers BD: Nature
of the glomerular capillary injury in human membranous glomerulonephritis. J Clin Invest 77: 868 877, 1986
2. Comper WD, Glasgow EF: Charge selectivity in kidney ultrafiltration. Kidney Int 47: 12421251, 1995
3. Orth SR, Ritz E: The nephrotic syndrome. N Engl J Med 338:
12021211, 1998
4. Peterson C, Madsen B, Perlman A, Chan AYM, Myers BD:
Atrial natriuretic peptide and the renal response to hypervolemia
in nephrotic humans. Kidney Int 34: 825 831, 1988
5. Perico N, Delaini F, Lupini C, Benigni A, Galbusera M, Boccardo
P, Remuzzi G: Blunted excretory response to atrial natriuretic peptide in experimental nephrosis. Kidney Int 36: 57 64, 1989
6. Remuzzi G, Bertani T: Pathophysiology of progressive nephropathies. N Engl J Med 339: 1448 1456, 1998
7. Black DAK, Rose G, Brewer DB: Controlled trial of prednisone
in adult patients with the nephritic syndrome. Br Med J 3:
421 426, 1979

J Am Soc Nephrol 12: S44 S47, 2001

8. Ponticelli C, Zucchelli P, Passerini P, Cagnoli L, Cesana B, Pozzi

C, Pasquali S, Imbasciati E, Grassi C, Redaelli B, Sasdelli M,
Locatelli F: A randomized trial of methylprednisolone and
chlorambucil in idiopathic membranous nephropathy. N Engl
Med J 320: 8 13, 1989
9. Falk RJ, Hogan SL, Muller KE, Jenette JC, Glomerular Disease
Collaborative Network: Treatment of progressive nephropathy:
A randomised trial comparing cyclophosphamide and corticosteroids with corticosteroids alone. Ann Intern Med 116: 438 445,
1992
10. Korbet SM, Schwartz MM, Lewis EJ: Primary focal segmental
glomerulosclerosis: Clinical course and response to therapy.
Am J Kidney Dis 23: 773783, 1994
11. Meyrier A, Simon P, Perret G, Condamin-Meyrier MC: Remission of idiopathic nephrotic syndrome after treatment with cyclosporine A. Br Med J 292: 789 792, 1986
12. Cattran DC, Appel GB, Hebert LA, Hunsicker LG, Pohl MA,
Hoy WE, Maxwell DR, Kunis CL: A randomised trial of cyclosporine in patients with steroid-resistant focal segmental glomerulosclerosis. Kidney Int 56: 2220 2226, 1999
13. Schieppati A, Mosconi L, Perna A, Mecca G, Bertani T, Garattini
S, Remuzzi G: Prognosis of untreated patients with idiopathic
membranous nephropathy. N Engl J Med 329: 85 89, 1993
14. Cattran DC, Greenwood C, Ritchie S, Bernstein K, Churchill
DN, Clark WF, Morrin PA, Lavoie S: A controlled trial of
cyclosporine in patients with progressive membranous nephropathy. Kidney Int 47: 1130 1135, 1995
15. Ambalavanan S, Fauvel J, Sibley RK, Myers BD: Mechanism of
the antiproteinuric effect of cyclosporine in membranous nephritis. J Am Soc Nephrol 7: 290 298, 1996
16. Mihatsch MJ, Kyo M, Morozumi K, Yamaguchi Y, Nickeleit V,
Ryffel B: The side-effects of cyclosporine A and tacrolimus. Clin
Nephrol 49: 356 363, 1998
17. McCauley J, Shapiro R, Ellis D, Igdal H, Tzakis A, Starzl TE:
Pilot trial of FK 506 in the management of steroid-resistant
nephritic syndrome. Nephrol Dial Transplant 8: 1286 1290,
1993
18. Budde K, Fritsche L, Neumayer HH: Differing proteinuria control with cyclosporin and tacrolimus. Lancet 349: 330, 1997
19. Deierhoi MH, Kauffman RS, Hudson SL, Barber WH, Curtis JJ,
Julian BA, Gaston RS, Laskow DA, Diethelm AG: Experience
with mycophenolate mofetil (RS 61443) in renal transplantation
in a single center. Ann Surg 217: 476 484, 1993
20. Nowack R, Birck R, van der Woude FJ: Mycophenolate mofetil
for systemic vasculitis and IgA nephropathy. Lancet 349: 774,
1997
21. Briggs WA, Choi MU, Scheel PJ: Successful mycophenolate
mofetil treatment of glomerular disease. Am J Kidney Dis 31:
213217, 1998
22. Zimmerman RF, Miller G, Radhakrishnan J, Appel GB: Mycophenolate mofetil treatment of membranous nephropathy [Abstract]. J Am Soc Nephrol 9: 103A, 1998
23. Al-Lehbi MA, Al-Maturi KA, Alfurayh AL: Mycophenolate
mofetil in steroid resistant focal segmental glomerulosclerosis
[Abstract]. J Am Soc Nephrol 10: 94A, 1999
24. Chen Y, Lu F, Li A, Zou W: Treatment of mycophenolate
mofetil combined with corticosteroid for membranous nephropathy stage II [Abstract]. J Am Soc Nephrol 10: 98A, 1999
25. Chen XM, Zang YP, Qiu QL, Cheng QL: Short-term effect of
mycophenolate mofetil on IgA nephropathy [Abstract]. J Am Soc
Nephrol 10: 69A, 1999

J Am Soc Nephrol 12: S44 S47, 2001

26. Radhakrishnan J, Wang M, Matalon A, Cattran D, Appel GB:

Mycophenolate mofetil treatment of idiopathic focal segmental
glomerular sclerosis [Abstract]. J Am Soc Nephrol 10: 114A,
1999
27. Maschio G, Alberti D, Janin G, Locatelli F, Mann IF, Motolese
M, Ponticelli C, Ritz E, Zucchelli P: Effect of the angiotensinconverting-enzyme inhibitor benazepril on the progression of
chronic renal insufficiency. N Engl J Med 334: 939 945, 1996
28. Plum J, Bnten B, Nemeth R, Grabensee B: Effect of the angiotensin II antagonist valsartan on blood pressure, proteinuria, and
renal hemodynamics in patients with chronic renal failure and
hypertension. J Am Soc Nephrol 9: 22232234, 1998
29. Wapstra FH, Navis G, De Jong PE, De Zeeuw D: Chronic
angiotensin II infusion but not bradykinin blockade abolishes the
antiproteinuric response to angiotensin-converting enzyme inhibition in established Adriamycin nephrosis. J Am Soc Nephrol
11: 490 496, 2000
30. Samuelsson O, Attman P-O, Knight-Gibson C, Larsson R, Mulec
H, Weiss L, Alaupovic P: Complex apolipoprotein B-containing
lipoprotein particles are associated with a higher rate of progression of human chronic renal insufficiency. J Am Soc Nephrol 9:
14821488, 1998
31. Kobashigawa JA, Katznelson S, Laks H, Johnson JA, Yeatman L,
Wang XM, Chia D, Terasaki PL, Sabad A, Cogert GA, Trosian K,
Hamilton MA, Moriguchi JD, Kawata N, Hage A, Drinkwater DC,
Stevenson LW: Effect of pravastatin on outcomes after cardiac
transplantation. N Engl J Med 333: 621 627, 1995
32. Katznelson S, Wilkinson AH, Kobashigawa JA, Wang X-M,
Chia D, Ozawa M, Zhong H-P, Hirata M, Cohen AH, Terasaki
PI, Danovitch GM: The effect of pravastatin on acute rejection
after kidney transplantation: A pilot study. Transplantation 61:
1469 1474, 1996
33. Thomas ME, Harris KPG, Ramaswamy C, Hattersley JM,
Wheeler DC, Zac Varghese JD, Williams JW, Moorhead JF:
Simvastatin therapy for hypercholesterinemic patients with nephrotic syndrome or significant proteinuria. Kidney Int 44:
1124 1129, 1993
34. Donker AJM, Brentjens JRH, van der Hem GK, Arisz L: Treatment of the nephrotic syndrome with indomethacin. Nephron 22:
374 381, 1978
35. Blume C, Heise G, Mhlfeld A, Bach D, Schrr K, Gerhardz D,
Grabensee B, Heering P: Effect of flosulide, a selective cyclooxygenase 2 inhibitor, on passive Heymann nephritis in the rat.
Kidney Int 56: 1770 1778, 1999
36. Kincaid-Smith P, Saker BM, Fairley KF: Anticoagulants in irreversible acute renal failure. Lancet 2: 1360 1363, 1968
37. Cade JR, de Quesada AM, Shires DL, Levin DM, Hackett RL,
Spooner GR, Schlein EM, Pickering MJ, Holcomb A: The effect
of long term high dose heparin treatment on the course of chronic
proliferative glomerulonephritis. Nephron 8: 67 80, 1971
38. Seiler MW, Rennke HG, Venkatachalam MA, Cotran RS: Pathogenesis of polycation-induced alterations (fusion) of glomerular epithelium. Lab Invest 36: 48 61, 1977
39. Striker L, Peten EP, Elliott SJ, Doi T, Striker GE: Mesangial cell
turnover: Effect of heparin and peptide growth factors. Lab
Invest 64: 446 456, 1991
40. Striker GE: Therapeutic uses of heparinoids in renal disease
patients. Nephrol Dial Transplant 14: 540 543, 1999
41. Flge J, Eng E, Young BA, Couser WG, Johnson J: Heparin
suppresses mesangial cell proliferation and matrix expansion in

Nephrotic Syndrome

42.

43.

44.

45.

46.

47.

48.

49.

50.

51.

52.

53.

54.

55.

56.

S47

experimental mesangioproliferative glomerulonephritis. Kidney

Int 43: 369 380, 1993
Gambaro G, van der Woude FJ: Glycosaminoglycans: Use in
treatment of diabetic nephropathy. J Am Soc Nephrol 11: 359
368, 2000
Tamsma JT, van der Woude FJ, Lemkes HHPJ: Effect of sulphated glycosaminoglycans on albuminuria in patients with overt
diabetic (type 1) nephropathy. Nephrol Dial Transplant 11: 182
185, 1996
Hoyer JR, Ray L, Vernier RL, Simmons RL, Najarian JS, Michael AF: Recurrence of idiopathic nephrotic syndrome after
renal transplantation. Lancet 2: 343348, 1972
Lagrue G, Branellec A, Niaudet P, Heslan JM, Guillot F, Lang P:
Transmission dun syndrome nphrotique deux nouveau-ns,
rgression spontane. Presse Med 20: 255257, 1991
Solomon LR, Cairns SA, Lawler W, Johnson RWG, Mallick NP:
Reduction of post-transplant proteinuria due to recurrent mesangial proliferative (IgM) glomerulonephritis following plasma exchange. Clin Nephrol 16: 44 50, 1981
Dantal J, Testa A, Bigot E, Soulillou JP: Disappearance of
proteinuria after immunoadsorption in a patient with focal glomerulosclerosis [Letter]. Lancet 336: 190, 1990
Dantal J, Bigot E, Bogers W, Testa A, Kriaa F, Jacques Y,
Hurault de Ligny B, Niaudet P, Charpentier B, Soulillou JP:
Effect of plasma protein adsorption on protein excretion in
kidney-transplant recipients with recurrent nephrotic syndrome.
N Engl J Med 330: 714, 1994
Hattori M, Ito K, Kawaguchi H, Tanaka T, Kubota R, Khono M:
Treatment with a combination of low-density lipoprotein apheresis and pravastatin of a patient with drug-resistant nephritic
syndrome due to focal segmental glomerulosclerosis. Pediatr
Nephrol 7: 196 198, 1993
Muso E, Yashiro M, Matsushima M, Yoshida H, Sawanishi K,
Sasayama S: Does LDL-apheresis in steroid-resistant nephritic
syndrome affect prognosis? Nephrol Dial Transplant 9: 257
264, 1994
Esnault VLM, Besnier D, Testa A, Coville P, Simon P, Subra JF,
Audrain MAP: Effect of protein A immunoadsorption in nephritic syndrome of various etiologies. J Am Soc Nephrol 10:
2014 2017, 1999
Koyama A, Fujisaki M, Kobayashi M, Igarashi M, Narita M: A
glomerular permeability factor produced by human T cell hybridomas. Kidney Int 40: 453 460, 1991
Savin VJ, Sharma R, Sharma M, McCarthy ET, Swan SK, Ellis
E, Lovell H, Warady B, Gunwar S, Chonko AM, Artero M,
Vincenti F: Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis. N Engl J Med 334: 878 893, 1996
McCarthy ET, Sharma R, Sharma M, Li J-L, Ge X-L, Dileepan
KN, Savin VL: TNF- increases albumin permeability of isolated rat glomeruli through the generation of superoxide. J Am
Soc Nephrol 9: 433 438, 1998
Henrich WL, Goldman M, Dotter CT, Bennett WN: Therapeutic
renal arterial occlusion for elimination of proteinuria. Arch Intern
Med 136: 840 842, 1976
Olivero JJ, Frommer JP, Gonzalez JM: Medical nephrectomy:
The last resort for intractable complications of the nephrotic
syndrome. Am J Kidney Dis 21: 260 263, 1993