1

PLASMAPHERESIS IN NEPHROLOGY
Voinov V.A.
I.P.Pavlov First Saint-Petersburg State Medical University, Saint-Petersburg, Russia

Abstract
Almost all chronic kidney disease in varying degrees, are associated with disorders of the
internal environment, mainly autoimmune nature. Drug therapy is not always effective and can
lead to additional disorders. Pathogenetically justified is the use of plasmapheresis.
Key words: kidney diseases, autoimmunity, plasmapheresis.
Almost all chronic kidney disease in varying degrees, are associated with disorders of the
internal environment of the body, mainly autoimmune nature. Moreover, the mechanisms of
these disorders varied.
So, glomerulonephritis is often a serious complication of streptococcal infection, when
toxins for elimination pathway distort the antigenic structure of the glomerular apparatus of the
kidney cells and provoke the formation of autoantibodies, which are fixed on the basement
membrane of the nephron with irreversible progressive defeat of the latter. Similarity of such
developments observed in rheumatism, confirmed by the fact that in 25% of cases did
glomerulonephritis combined with rheumatism.
Given the autoimmune nature of the disease, it is expedient to possible early
plasmapheresis starting with the first signs of its occurrence [1], although it is often resorted to
plasmapheresis only when steroid-resistant forms of glomerulonephritis [2, 3].
Retrospective analysis of treatment of 48 children with idiopathic rapidly progressive
glomerulonephritis, and renal or nonrenal vasculitis undergoing plasmapheresis background
courses prior ineffective treatment with corticosteroids and cytotoxic drugs, showed significant
improvement in renal function in 58% of patients and long-lasting positive effects in all patients
with vasculitis [4, 5, 6].
Similar results achieved also Yu.V. Komyagin and Yu.S. Milovanov [7], 18 patients with
rapidly progressive glomerulonephritis associated with systemic lupus, hemorrhagic vasculitis,
Wegener's granulomatosis, microscopic polyarteritis, and using the rates of 5-10 treatments
plasmapheresis with removal per session 1.5-2 liters of plasma. It is possible to stabilize or
improve during the process and increase renal survival. Of course, keep in mind that
glomerulonephritis, as well as any other autoimmune pathology, can not be completely cured and
requires systematic courses of plasmapheresis throughout life. In such cases, the interruption of
treatment, patients inevitably become dialysis-dependent or require transplantation.

2
Especially shown an efficiency of inclusion of plasmapheresis in the treatment of
glomerulonephritis on a background of nephrotic syndrome [8]. G.E. Russo et al. [9] used this
technique in a cascade plasma filtration cycles with 3 sessions and after the last infusion of
prednisolone (300 mg/kg) and the repetition of such courses on a monthly basis for six months,
which can significantly reduce the degree of proteinuria and steadfastly improve kidney function.
T. Kobayashi et al. [10] described a case where with steroid treatment of nephrotic
syndrome in patients undergoing hepatitis B, developed hepatic failure. Subsequently applied
cascade plasmapheresis monotherapy treatments to 9, resulting in reduction in proteinuria of 9.2
g/day to 0.2 g/day and this state was maintained after 12 months.
Nevertheless, only the timely removal of antibodies be able to prevent or at least reduce the
degree of parenchymal renal organic damage. The same tactic is justified also at the subsequent
exacerbations even have any manifestations of renal failure, to distant prospect for the transition
to chronic hemodialysis .
So P.A.Vorobev and B.A.Aynabekova [11] reported the use of plasmapheresis in 10 patients
in the conservative phase of chronic renal failure when glomerular filtration still maintained at
10-15 ml / (minm2). Indications were signs of uremic toxicity (fatigue, nausea), pruritus,
hypertension. After a course of 5 sessions of plasmapheresis noted rapid improvement in health
with a decrease in blood pressure, the disappearance of itching, decreased serum creatinine and
urea, increase in glomerular filtration rate. In such cases, plasmapheresis allowed to push the
date of transfer of patients on chronic hemodialysis.
But even with a complete loss of kidney function, hemodialysis is not able to provide
remove all pathological of compounds, particularly molecular weight of more than 1000 Daltons,
ie, middle weight molecules, which do not pass through the dialysis membrane known, but cause
a number of adverse metabolic disorders, among which more than just worried sick, itchy skin.
In varying degrees, expressed it occurs in 60-90% of patients during hemodialysis. Its
pathogenesis depends of many metabolic factors hypercalcemia, hyperphosphatemia,
secondary hyperparathyroidism, hypermagneziemiya.
But even in the absence of metabolic disorders pruritus was significantly disturbed daily
activity and nocturnal sleep [12]. In such cases, obviously, hemodialysis is simply not able
enough to fully withdraw all products pathological metabolic and periodic addition of
plasmapheresis can greatly improve the quality of life of these patients. In particular, acute
kidney failure with glomerulonephritis plasmapheresis in conjunction with hemodialysis
facilitated more rapid relief of clinical symptoms and the achievement of stable remission [13].
There is used also a "tandem method" simultaneous hemodialysis and plasmapheresis. At first
the blood pass through the plasma filter, and then through the dialyzer [14].

3
In chronic hemodialysis often develop anemia, are not always amenable to erythropoietin
administration and iron supplementation (Sorbifer). In such cases, periodic plasmapheresis
helped stabilize hemoglobin levels and increased intervals between the infusions of packed red
blood cells up to 6 months [15].
In essence, and any other form of renal parenchymal lesions (nephrosis or nephritis exo- or
endotoxin genesis, lupus nephritis) efferent therapy can prevent or reduce the disease occurred
[16]. Of course, not every acute renal pathology becomes chronic, but predict in advance such a
situation is practically impossible, so even preventive perform in general completely safe
procedure plasmapheresis seems justified, even in childhood. Especially when you consider that
neither age nor body weight, have not additional restrictions for membrane plasmapheresis.
The kidneys are the target organ in a wide variety of autoimmune diseases, particularly
such as systemic lupus erythematosus (lupus nephritis), Goodpasture's syndrome, purpura
Henoch-Shenlyayn, Wegener's granulomatosis, polyarteritis nodosa, in which is an important
component of the pathogenesis of vasculitis.
The most common periarteritis nodosa, which is a generalized autoimmune necrotizing
inflammation of the endothelium and the middle layer of medium and small arteries as a result of
antigen-antibody reactions. Emerging granulomatosis while sometimes called rash at vessels.
The clinical picture depends on the primary lesion of any organ of the abdominal or thoracic
cavity, brain, limbs. Renal artery aneurysms with expanded with thrombosis and ruptures,
leading to heart attacks and kidney hemorrhage. In another form of the disease "microscopic"
polyarteritis affects mainly small arteries with the development of necrotizing
glomerulonephritis. Perhaps the development also renal amyloidosis with proteinuria and renal
insufficiency [17]. In the treatment of this disease, along with steroid therapy was used the
plasmapheresis also [18].
Granulomatous angiitis is a kind of Wegener's granulomatosis with severe lesions of both
lungs, and kidneys, oral ulcers and nose. It is also possible involvement of the nervous system,
skin, muscle, and even heart failure. Sufficiently sensitive and specific markers of the disease, as
well as "microscopic polyangiitis" (Horton's disease), is the detection of anti-neutrophil
cytoplasmic autoantibodies (ANCA), especially in the period of exacerbation.
Immunosuppressive therapy significantly reduces mortality in patients with systemic
vasculitis, but morbidity remains sufficiently high because of the frequent exacerbations even
iatrogenic complications including infections [6,19]. Development of rapidly progressive
glomerulonephritis and diffuse alveolar hemorrhage is an indication for plasmapheresis [5, 6, 8,

4
20, 21, 22, 23, 24, 25, 26, 27]. In such cases there is performed also cascade plasmapheresis [28].
Kidney transplantation in these patients is possible only after reducing the titer ANCA.
Goodpasture's syndrome hyperergical angiitis as a form of pulmonary-renal syndrome.
It is an autoimmune disease characterized by infiltration of the lung tissue with bleeding and
hemoptysis, moreover, autoantibodies affect the glomerular basement membrane with renal
hematuria, anemia and the development of glomerulonephritis. The prognosis for this disease is
bad mortality within 6 months from the onset of the disease is about 21% [29]. There was
described the successful treatment of multiple sessions of plasmapheresis with regression of
disorders, confirmed clinically and laboratory data, and radiological studies [30, 31, 32, 33].
Plasmapheresis in patients with hemorrhagic vasculitis leads to normalization of coagulation
potential, increase the activity of antithrombin III, a decrease in content of products of
paracoagulation, accelerate fibrinolysis and normalize platelet aggregation. There is decreased
the level of circulating immune complexes, IgA, and IgE. This is accompanied by clinical signs
of regression the vascular disorders also [34]. IgG antibodies to glomerular basement membrane
of nephron can be also significantly reduced by 24% using a cascade plasmapheresis. Its
subsequent sessions lead to their reduction to 52%, 57% and 60% [35]. In the UK Goodpasturs
syndrome is a direct indication for plasma exchange [36].
Lupus nephritis is an irreversible progressive glomerular lesion, causing generally die in
this disease [37]. The frequency of its development of SLE patients is 60-70%. Renal glomeruli
affected antinuclear autoantibodies (ANA), which accumulate in the walls of capillaries and
mesangium [38]. Massive deposition of immune complexes in the blood vessels of the kidneys
can develop without signs of active lesions of glomeruli [39].
Nevertheless, efferent therapy (in the background, of course, hormonal therapy, and
cytostatics) plasmapheresis courses per year to two allows for a long period to slow the
progression and even maintain operability of patients. There is used also tactics three
consecutive daily sessions of plasmapheresis (to remove the intra- and extravascular antibodies),
with three consecutive intravenous pulse cyclophosphamide (400 mg/m2 x 3), then prednisone
with the transition to its maintenance doses [40; 41]. In some cases it was optimal rate of
monthly plasmapheresis [Clark W.F. et al., 1981]. Striking effect was obtained when applying
course of cascade plasmapheresis ( 7 sessions over 2 weeks), which led to the complete
disappearance of proteinuria [42].
In recent years, began to use calcineurin inhibitors (tacrolimus) [43], but we must take into
account the negative consequences of its use mainly nephrotoxic [44], which is especially
dangerous at high risk for lupus nephritis.

5
Cryoglobulinemia is characterized by the appearance in the circulation of cold
precipitating cryoglobulins with their deposition in the walls of small blood vessels, including
the kidney (capillaries, arterioles and venules) and symptoms of systemic vasculitis that
promotes also the glomerulonephritis [45].
Plasmapheresis plays an important role in the treatment of cryoglobulinemia [46, 47, 48],
especially if other methods of correction are ineffective [49]. There is used with the success and
the technology of the cascade plasmapheresis [50, 51]. Thus A. Ramunni et al. [52] performed
30 sessions of cascade plasmapheresis for 6 months and have not only complete healing of
venous ulcers arising on the basis of cryoglobulinemia, but a significant decrease in the amount
of HCV RNA in the blood.
Paraproteinemic hemoblastoses a group of diseases characterized by monoclonal
proliferation of B-lymphocytes secreting immunoglobulins [Ansell 53]. First of all, they include
multiple myeloma and Waldenstrom's macroglobulinemia. At the same time there is
developing a nephropathy also. The method of choice is a course of plasmapheresis daily until
stabilization of controllable indicators (total protein, blood viscosity), in the future repeat
procedure 1-2 times a week while maintaining hyperviscous syndrome [54, 55, 56].
Myeloma cast nephropaty develops due to the delay in the renal tubules of light protein
chains (M-protein) with progressive renal failure that determines the indications for
plasmapheresis, and approved also by the International Community of myeloma (International
Myeloma Foundation) [57, 58, 59, 60, 61].
B.T.Ciccarelli et al. [62] noted that if rituximab induced rise of IgM content from 3515 to
5270 mg/dL, the plasmapheresis helped to reduce it from 6940 to 4770 mg\dl. S.M.Ansell et al.
[53] believed that all patients with symptoms of high blood viscosity should be first subjected to
treatment with plasmapheresis.
IgA nephropathy is the most common cause of glomerulonephritis with impaired
glomerular filtration rate, proteinuria and high uncontrolled hypertension [63].
Kidney suffered also by diabetes diabetic nephropathy is the leading cause of chronic
renal failure requiring hemodialysis. Diabetic nephropathy is left on one of the first places
among the causes of chronic renal insufficiency needed of dialysis. Patients with diabetes first
type in Europe and the U.S. is about half of undergoing hemodialysis [64]. There is direct
toxicity of elevated glucose concentrations for nephron structures with concomitant lipid
disorders (frequent lipid deposits in the kidneys) and subsequent sclerotic changes mesangium

6
cells, together with deposits of circulating immune complexes that underlie renal parenchymal
lesions in diabetes.
There attention is paid to the role of "vascular endothelial growth factor" as multifunctional
cytokine also known as vascular permeability factor in the development of the micro- and
macrovascular diabetic complications, particularly diabetic retinopathy and nephropathy [65]. If
diabetes mellitus type 1 immune complex glomerulonephritis is characteristic, then for diabetes
type 2 atherosclerotic nephro-angiosclerosis.
Due to the increase in vascular permeability at the earliest signal nephropathy development
of such pathology is the detection of microalbuminuria (concentration 30-200 mg/l, or with
excretion rate 20-200 micrograms min), which can be detected in 29-41% of diabetics with
disease duration of more than 5-7 years [66]. 70% of diabetics suffer with microalbuminuria and
hypertension, which strengthens this relationship diabetes and nephropathy. In the United States,
except for one million patients with diabetes type 1 and 13 million patients with diabetes mellitus
type 2, there are still about 6 million people who have this form of diabetes remain undiagnosed.
We

must

assume

that

in

Russia

this

is

not

the

best

way.

Therefore, in all these cases is pathogenetically justified plasmapheresis treatment and

prevention of progression of renal lesions [8]. Indeed, the use of plasmapheresis background
immunosuppressant quickly stabilizes renal function with cessation of progression of renal
failure [7]. At the same time, often requires the removal of very massive plasma volumes up to
2-2.5 liters (1 CPV), 3 first such session in a day, then 2-3 sessions every 2 weeks [67].
Renal disease also occurs in amyloidosis, sarcoidosis, psoriasis, gout [68].
Focal segmental glomerulosclerosis leads to severe steroid-resistance nephrotic syndrome
with severe proteinuria [68, 69]. Plasmapheresis may reduce proteinuria, until its complete
remission [70]. And there is often recurs after kidney transplantation [71]. In such cases,
plasmapheresis carried out for a long time (up to 133 sessions over 35 months) weekly before the
next administration of rituximab [72, 73, 74, 75]. Plasmapheresis performed before kidney
transplantation to remove antibodies, is helping to reduce the recurrence rate to 26% against 54%
in the control group [76].
The most common tactic for treatment of autoimmune diseases is based on a two-drug
therapy corticosteroids and cytotoxic drugs. They are designed to delay reproduction clones of
autoreactive T- and B-lymphocytes. Substantially reduced immunosuppressive therapy makes Tsuppressor function.

7
However, this therapy is not without a large number of side reactions. Corticosteroids cause
Cushingoid syndrome. Glucocorticoids are in particular due to the diabetogenic hormone
suppression of tissue glucose uptake and increase its production by the liver.
Another complication of prolonged glucocorticoid therapy is osteoporosis. It is believed
that these hormones inhibited the proliferation and differentiation of osteoblasts that stimulate
apoptosis. There are also indirect mechanisms of bone resorption as a result of secondary
hyperparathyroidism due to reduced absorption of calcium in the intestine. Cytostatics lead to
significant metabolic disorders, including healthy organs and systems.
Frequently used was large intravenous doses of immunoglobulins lead to a significant
reduction in the pathological autoantibodies inhibitors, and this effect is greater than the period
of life of these immunoglobulins, which means a more significant correction regulatory
autoimmune pathological processes in the body of patients.
However, under intense IVIG there was described a greater number of complications. Most
often lead Infections patients with hepatitis G [77, 78]. It is possible development of acute renal
failure after an immunoglobulin therapy [79]. It is also described and serious complications such
as vasculitis and lupus because of the side effects introduced together with immunoglobulins and
associated autoantibodies and circulating immune complexes, lethal hypersensitivity, not to
mention the transmission of hepatitis viruses C and D, etc. [80]. It is noted and significant
increase in blood viscosity at high doses of immunoglobulins, which can create several problems
in older patients at the presence of vascular diseases in cryoglobulinemia, monoclonal
gammopathy, high levels of lipoproteins [81].
Should take into account the fact that immunoglobulin is nothing like most complexes of
different antibodies. Among them are not only valuable to the health of antibodies against a
variety of bacteria and viruses, to which donors had on different segments of their life go into
opposition, but autoantibodies against antigens own structures. And even if they are formally
considered healthy donors, however, are not excluded latent proceeding and had not yet
manifested symptoms of those or other diseases. With intensive immunoglobulin therapy they
simultaneously input from many donors and the total number of some autoantibodies may
exceed a certain critical mass of more manifest pathology. At the same time such a mass of
immunoglobulins instead of "concentrate of health" can turn into "concentrate of disease."
In recent years, became widespread treatment of autoimmune diseases with rituximab
chimeric monoclonal antibody to the CD20 antigen of B-lymphocytes, which would reduce the
production of autoantibodies [73]. Nevertheless, there were described and complications of such
treatment until the development of multiple organ failure [82].

8
One should also consider that with age increases the risk of renal lesions associated with
disorders of biochemical and immune homeostasis. In particular, the growing number of patients
suffering from the metabolic syndrome with disorders of lipid metabolism, hypertension and
type 2 diabetes. All this is accompanied by the development of diabetic nephropathy, which is
often as severe, requiring hemodialysis. Despite the maintenance of blood sugar levels, thus
there is microvascular endothelial damage accumulating substances which are not amenable to
drug therapy [83].
On the other hand, there are vascular disorders associated with atherosclerosis due to
narrowing of the lumen of blood vessels, including the renal, and also not always amenable to
drug therapy. And stent placement or bypass surgery of the coronary vessels can not be used for
correction of the renal vessels. Amyloid deposits are common in the intercellular spaces,
including the formation of the so-called senile plaques that 60% of older age characteristic
feature appears. All this is accompanied by a picture of renal amyloidosis also.
With age, growing and autoimmune disorders accompanied by systemic lesions of different
organs, including the kidney. Especially for different types of systemic vasculitis affecting the
kidneys vessels. Characteristic of old age is the appearance of signs of paraproteinemia with
accumulation of monoclonal immunoglobulin M-components resembling now myeloma.
Increases the content of cryoglobulins also. All this is largely disturbed microcirculation,
including at the level of the glomeruli.

With age increases the frequency of hepatitis C virus

infection in which there is autoimmune hepatitis, which is often accompanied by renal outcomes.
So more and more clearer picture of disorders of homeostasis, leading to progressive organ
disorders. At the same time there is an accumulation of many pathological products, the size of
molecules that do not allow them to pass through the kidney, the liver does not destroy them. On
the other hand, the fact of their accumulation suggests that no drugs were able to help in their
removal from the body. Interrupt these vicious circles interdependent violations can only be
timely remove of pathological products from the body that is able to completely solve only
efferent therapy, mainly plasmapheresis.
In this connection we would like to repeat the well-known truth many diseases are easier
to prevent than to treat their consequences. Therefore, it may be reasonable to preventive courses
of plasmapheresis, even in apparently healthy people have reached the age of forty, after which
significantly increases the risk of disorders of the internal environment.
Conclusion

9
The above material makes ponder and weigh almost secure (in the right hands)
plasmapheresis procedure and above danger of ntensive immunoglobulin therapy, especially
when you consider that report them to doctors, medicines which enjoyed the reputable European
pharmaceutical firms. The same applies to the various options of hormonal and cytotoxic
therapy.
Therefore, only plasmapheresis is able to remove not only the immune complexes and
autoantibodies, but the biochemical and other pathological products of homeostasis, thereby
normalizing the basic metabolic processes. It should be borne in mind that the high molecular
weight compounds such as autoantibodies and immune complexes kidneys are not able to
excrete and can be removed from the organism almost exclusively via plasmapheresis .
And only after the restoration of biochemical and immune homeostasis can and should
carry medication or non-drug therapy, the appropriate view of these diseases, using significantly
lower doses of these drugs.

References
1. Haris A., Arnyi J., Braunitzer H. et al. {Role of plasmapheresis in immunological
kidney diseases. Experience from 1050 completed plasmapheresis treatment sessions] // Orv.
Hetil. 2011. Vol. 152, 28. P. 1110-1119.
2. Artero M.L., Sharma R. et al. Plasmapheresis reduces proteinuria and serum capacity to
injure glomeruli in patients with recurrent focal glomerulosclerosis // Am. J. Kid. Dis. 1994.
23. P. 574-581.
3. Ginsburg D.S., Dau P. Plasmapheresis in treatment of steroid-resistant focal segmental
glomerulosclerosis // Clinical Nephrology. -1997. -Vol. 48, 5. - P. 282-287.
4. Madore F. Plasmapheresis. Technical aspects and indications // Crit. Care Clin. 2002.
Vol. 18, 2. P. 375-392.
5. Walters G.D., Willis N.S., Craig J.C. Interventions for renal vasculitis in adults. A
systematic review // BMC Nephrol. 2010. . 11. P. 12.
6. Walsh M., Catapano F., Szpirt W. et al. Plasma exchange for renal vasculitis and
idiopathic rapidly progressive glomerulonephritis: meta-analysis // Am. J. Kidney Dis. 2011.
Vol. 57, 4. P. 566-574.
7. Komyagin Yu.V., Milovanov Yu.S. [Plasmapheresis in the treatment of patients with
rapidly progressive glomerulonephritis in systemic diseases] / Proc. VIII Confer. Moscow
hemaoheresis society. M., 2000. P.31. (Rus).
8. Shelukhin V.A., Kostjuchenko A.L. [Efferent therapy in renal diseases and injuries // In:
Efferent Therapy / Ed. A.L.Kostyuchenko. St. Petersburg: Folio, 2003. P. 268-302.
9. Russo G.E., Caramiello M.S., Vitaliano E. et al. Haemorheological changes in mixed
cryoglobulinaemia during apheresis treatment // Transfus. Sci. 1996. Vol. 17. P. 499-503.
10. Kobayashi T., Ando Y., Umino T. et al. Complete remission of minimal-change
nephrotic syndrome induced by apheresis monotherapy // Clin. Nephrol. 2006. Vol. 65, 6.
P. 423-426.
11. Vorobyev P.A., Ainabekova B.A. [Plasmapheresis therapy in place of the initial stages of
CKD] / Proc. V Confer. Moscow hemapheresis society. M., 1997. P. 57. (Rus).

10
12. Goicoechea M., de Sequera P., Ochando A. et al. Uremic pruritus: an unresolved
problem in hemodialysis patients // Nephron. 1999. Vol. 82, 1. P. 73-74.
13. Zverev D.V., Tebloeva L.T., Emirova H.M., Yurkiv I.J. [Treatment of children with
glomerulonephritis complicated by acute renal failure] / Proc. IX Conf. Moscow hemapheresis
society. M., 1999. P. 128. (Rus).
14. Dechmann-Sultemeyer T., Linkeschova R., Lenztn K. et al. Tandem plasmapheresis and
haemodialisis as a safe procedure in 82 patients with immune-mediated disease // Nephrol. Dial.
Transplant. 2009. Vol. 24, 1. P. 252-257.
15. Petrova V.I., Julakyan U.L., Fedorova L.N. et al. [Effective plasmapheresis in patients
with anemia of chronic disease] / Proc. XX Conf. Moscow hemapheresis society. Dubna.
2012. - Pp. 102-103. (Rus).
16. Loo C.Y., Mohamed Said M.S., Mohd R. et al. Immunoadsorption and plasmapheresis
are equally efficacious as adjunctive therapies for severe lupus nephritis // Transfus. Apher. Sci.
2010. Vol. 43, 3. P. 335-340.
17. Yorioka N., Tanigichi Y., Okushin S. et al. Classic polyarteritis nodosa associated with
renal amyloidosis // Nephron. 1999. Vol. 82, 1. P. 93-94.
18. Chen K.R., Carlson J.A. Clinical approach to cutaneous vasculitis // Am. J. Clin.
Dermatol. 2008. Vol. 9., 2. P. 71-92.
19. Kyndt X., Reumaux D., Bridoux F. et al. Serial measurements of antineutrophil
cytoplasmic autoantibodies in patients with systemic vasculitis // Am. J. Med. 1999. Vol. 106,
5. P. 527-533.
20. Klemmer P.J., Chalermskulrat W., Reif M.S. et al. Plasmapheresis therapy for diffse
alveolar hemorrhage in patients with small-vessel vasculitis // Am. J. Kidney Dis. 2009. Vol.
42, 6. P. 1149-1153.
21. De Groot K., Reinhold-Keller E. Wegeners granolomatosis and microscopic
polyangiitis // Z. Rheumatol. 2009. B. 68, 1. S. 49-63.
22. Picard C., Parrot A., Mayaud C., Cadranel J. Diffuse alveolar hemorrhage in the
immunocompetent host: diagnostic and therapeutic management // Presse Med. 2009. Vol.
38, 9. P. 1343-1352.
23. Bolton W.K. Pulmonary renal syndrome and emergency therapy // Contrib. Nephrol.
2010. Vol. 165. P. 166-173.
24. Villiger P.M., Guillevin L. Microscopic polyangiitis: Clinical presentation //
Autoimmun. Rev. 2010. Vol. 9, 12. P. 812-819.
25. Gregersen J.W., Kristensen T., Krag S.R. et al. Early plasma exchange improves
outcome in PR3-ANCA-positive renal vasculitis // Clin. Exp. Rheumatol. 2012. Vol. 30, 1
(Suppl 70). P. S39-47.
26. Sinico R.A., Di Toma L., Radice A. Renal involvement in anti-neutrophil cytoplasmic
autoantibody associated vasculitis // Autoimmu. Rev. 2013. Vol. 12, 4. P. 477-482.
27. Sugiyama K., Sada K., Kurosawa M. et al. Current status of the treatment of
microscopic polyangiitis and granulomatosis with polyangiitis in Japan // Clin. Exp. Nephrol.
2013. Vol. 17, 1. P. 51-58.
28. Isoda K., Nuri K., Shoda T. et al. Microscopic polyangiitis complicated with cerebral
infarction and hemorrhage: a case report and review of literature // Nihon Rinsho Meneki Gakkai
Kaishi. 2010. Vol. 33, 2. P. 111-115.
29. Hirayama K., Yamagata K., Kobayashi M., Koyama A. Anti-glomerular basement
membrane antibody disease in Japan: part of the nationwide rapidly progressive
glomerulonephritis survey in Japan // Clin. Exp. Nephrol. 2008 Vol. 12, 5. P. 339-347.
30. Delogu L.G., Deidda S., Delitala G., Manetti R. Infectious diseases and
autoimmunity // J. Infect. Dev. Ctries. 2011. Vol. 5, 10. P. 679-687
31. Risso J.A., Mazzochi O., De All J., Gnocci C.A. Pulmonary-renal syndrome // Medicina
(B. Aires) . 2009. Vol. 69, 6. P. 663-673.

11
32. Cigarrn S., Castro M.J., Pousa M. et al. Plasmapheresis in diffuse alveolar
hemorrhage as perinuclear antineutrophil cytoplasmic antibody-associated vasculitis relapse on
hemodialysis // Ther. Apher. Dial. 2010. Vol. 14, 3. P. 368-372.
33. Prez-Surez G., Marrero D., Rodrguez R. et al. Goodpastures syndrome with
neurologic involvement and negative ANCA // Nefrologia. 2010. Vol. 30, 5. P. 584-587.
34. Marsagishvili M.A., Kalinin N.N., Model S.V. et al. [Therapeutic efficacy of
plasmapheresis in patients with hemorrhagic vasculitis] / Proc. VII Conf. Moscow hemapheresis
society. M., 1999. - P. 102. (Rus).
35. Hajima N., Michiko A., Atsunori K. et al. A case report of efficiency of double filtration
plasmapheresis in treatment of Goodpastures syndrome // Ther. Apher. Dial. 2009. Vol. 13,
4. P. 373-377.
36. Thompson G.R. Therapeutic apheresis in UK // . 2013. .
19, 1. . 35.
37. Lewis E.J., Hunsicker L.G., LAN S.-P. et al. A controlled trial of plasmapheresis therapy
in severe lupus nephritis // New Engl. J. Med. - 1992. - Vol. 326, 21. - P. 1373-1379.
38. Seery J.P., Carroll J.M., Cattell V., Watt F.M. Antinuclear autoantibodies and lupus
nephritis in transgenic mice expressing interferon in the epidermis // J. Exp. Med. - 1997. - Vol.
186, 9. - P. - 1451-1459.
39. Takazoe K., Shimada T., Nakano H. et al. Massive uncomplicated vascular immune
complex deposits in the kidney of a patient with systemic lupus erythematosus // Clin. Nephrol. 1997. - Vol. 48, 3. - P. 195-198.
40.
Demin A.A., Sentyakova T.N., Smirnov V.V. et al. [Synchronizing plasmapheresis
and cyclophosphamide therapy of rapidly progressive systemic lupus erythematosus] // Ther.
Arch. (Rus). 1996. Vol. 68, 5. P. 27-30 .
41. Yamaji K., Kim Y.J., Tsuda H., Takasaki Y. Long-term clinical outcomes of
synchronized therapy with plasmapheresis and intravenous cyclophosphamide pulse therapy in
the treatment of steroid-resistant lupus nephritis // Ther. Apher. Dial. 2008. Vol. 12, 4. P.
298-305.
42. Agishi T., Kaneko I., Hasuo Y. et al. Double Filtration plasmapheresis // Ther. Apher.
2000. Vol. 4, 1. P.29-33.
43. Yoon K.H. Efficacy and cytokine modulating effects of tacrolimus in systemic lupus
erythematosus: a review // J. Biomed. Biotechnol. 2010. 686480.
44. Hesselink D.A., Bouamar R., van Gelder T. The pharmacogenetics of calcineurin
inhibitor-related nephrotoxicity // Ther. Drug Monit. 2010. Vol. 32, 4. P. 387-393.
45. Ferri C. Mixed cryoglobulinemia // Or[hanet J. Rare Dis. 2008. Vol. 3 P. 25.
46. Russo G.E., Bonello M., Bauco B. et al. Nephrotic syndrome and plasmapheresis // Int.
J. Artif. Organs/ - 2000. Vol. 23, 2. P. 111-113.
47. Dominguez J.H., Sha E. Apheresis in cryoglobulinemia complicating hepatitis C and in
other renal diseases // Ther. Apher. 2002. Vol. 6. P. 69-76.
48. Scarpato S., Tirri E., Naclerio C. et al. Plasmapheresis in cryoglobulinemic
neuropathy: a clinical study // Dig. Liver. Dis. 2007. Vol. 39, Suppl. 1. P. S136-137.
49. Pietrogrande M., De Vita S., Zignego A.L. et al. Recommendations for the management
of mixed cryoglobulinemia syndrome in hepatitis C virus-infected patients // Autoimmun. Rev.
2011. Vol. 10, 8. P. 444-454.
50. Valbonesi M., Bo A., De Luidgi M.C. et al. Cascade filtration (CF) with the
Haemonetics MCS+: a new technical adaptation // Int. J. Artif. Organs. 2001. Vol. 24, 3.
P. 164-166.
51. Struk J., Taborski U., Neeck G. Essential cryoglobulinemic vasculitis with severe
peripheral neuropathy and neurogenic muscular atrophy inducing remission by cascade
filtration // Z. Rheumatol. 2002. Vol 61, 6. P. 733-739.

12
52. Ramunni A., Lauletta G., Brascia P. et al. Double-filtration plasmapheresis in the
treatment of leg ulcers in cryoglobulinemia // J. Clin. Apher. 2008. Vol. 23, 3. P. 118122.
53. Ansell S.M., Kyle R.A., Reeder C.B. et al. Diagnosis and management of Waldenstrm
macroglobulinemia: Mayo stratification of macroglobulinemia and risk-adapted therapy
(mSMART) guidelines // Mayo Clin. Proc. 2010. Vol. 85, 9. P. 824-833.
54. Kalinin N.N., Movshev B.E., Petrov M.M. [Monitoring and other protein-volemic
indicators in plasmapheresis in patients with paraproteinemy] // Ther. Arch. (Rus). 1996.
Vol. 68, 7. P. 62-65.
55. Stone M.J. Waldenstrms macroglobulinemia: hyperviscosity syndrome and
cryoglobulinemia // Clin. Lymphoma Myeloma. 2009. Vol. 9, 1. P. 97-99.
56. Treon S.P. How I treat Waldenstrm macroglobulinemia // Blood. 2009. Vol. 114,
12. P. 2375-2385.
57. Durie B.G., Kyle R.A., Belch A. et al. Myeloma management guidelines: a consensus
report from the Scientific Advisors of the International Myeloma Foundation // Hematol. J.
2003. Vol. 4. P. 379-398.
58. Clark W.F., Lindsey R.M., Caltran D.C. et al. Monthly plasmapheresis for systemic
lupus erythematosus with diffuse proliferative glomerulonephritis: a pilot study // Can. Med.
Assoc. J. 1981. Vol. 125, 2. P. 171-174.
59. Cserti C., Haspel R., Stowell C., Dzik W. Light-chain removal by plasmapheresis in
myeloma-associated renal failure // Transfusion. 2007. Vol. 47. P. 511-514.
60. Kleeberg L., Morgera S., Jacob C. et al. Novel renal replacement strategies for the
elimination of serum free light chains in patients with kappa light chain nepfropaty // Eur. J.
Med. Res. 2009. Vol. 14, 2. P. 47-54.
61. Gupta D., Bachegowda L., Phadke G. et al. Role of plasmapheresis in the management
of myeloma kidney: a systematic review // Hemodial. Int. 2010. Vol. 14, 4. P. 355-363.
62. Ciccarelli B.T., Yang G., Hatjiharissi E. et al. Soluble CD27 is a faithful marker of
disease burden and is unaffected by the rituximab-induced IgM flare, as well as by
plasmapheresis, in patients with Waldenstrms macroglobulinemia // Clin. Lymphoma
Myeloma. 2009. Vol. 9, 1. P. 56-58.
63. Mertens P.R., Floege J. [IgA-nephropathy: the most common type of
glomerulonephritis[ // Dtsch. Med. Wochenschr. 2003. B. 128, 22. S. 1242-1246.
64. Sura V.V., Borisov I.A., Kamaeva O.I., Filippova V.G. [Diabetic and gouty nephropathy
(some aspects of) // Ther. Arch. (Rus). 1995. Vol. 67, 8. P. 3-5.
65. Duh E., Aiello L.P. Vascular endothelial grows factor and diabetes. The agonist versus
antagonist paradox // Diabetes. 1999. Vol. 48, 10. P. 1899-1906.
66. Mattock M.B., Barness D.J., Viberti GC. et al. Microalbuminuria and coronary heart
disease in NIDDM. An incidence study // Diabetes. 1998. Vol. 47, 11. P. 1786-1792.
67. Milovanov Y.S. [Plasmapheresis in nephrology] / In. "Clinical application of
extracorporeal therapies." M., 2006. - P. 72-75. (Rus).
68. McCarthy T., Sharma M., Savin V.J. Circulating permeability factors in idiopatic
nephritic syndrome and focal segmental glomerulosclerosis // Clin. J. Am. Soc. Nephrol. 2010.
Vol. 5. P. 2115-2121.
69. DAgati V.D., Kaskel F.J., Falk R.J. et al. Focal segmental glomerulosclerosis // N.
Engl. J. Med. 2011. Vol. 365. P. 2398-2411.
70 Garcia C.D., Bittencourt V.B., Tumelero A. et al. Plasmapheresis for recurrent
posttransplant focal segmental glomerulosclerosis // Transplant. Proc. 2006. Vol. 38. P.
1904-1905.
71. Keith D.S. Therapeutic apheresis rescue mission: recurrent focal segmental
glomerulosclerosis in renal allografts // Semin. Dial. 2012. Vol. 25. P. 190-192.
72. Passerini P., Scolari F., Frasca G.M. et al. How to treat patients with focal segmental
glomerular sacerosis // G. Ital. Nephrol. 2009. Vol. 26, 5. P. 564-576.

13
73. Rodriquez-Ferrero M., Ampuero J., Anaya F. Rituximab and chronic plasmapheresis
therapy of nephrotic syndrome in renal transplantation patients with recurrent focal segmental
glomerulosclerosis // Transplant. Rroc. 2009. Vol. 41, 6. P. 2406-2408.
74. Gonzalez E., Ettenger R., Rianthavorn P. et al. Preemptive plasmapheresis and
recurrence of focal segmental glomerulosclerosis in pediatric renal transplantation // Pediatr.
Transplant. 2011. Vol.15. P. 495-501.
75. Gungor O., Sen S., Kircelli F. et al. Plasmapheresis therapy in renal transplant patients:
five-year experience // Transplant. Proc. 2011. Vol.43. P. 853-857.
76. Gohh R.Y., Yango A.F., Morrissey P.E. et al. Preemptive plasmapheresis and recurrence
of FSGS in high-risk renal transplant recipients // Am. J. Transplant. 2005. Vol. 5. P. 29072912.
77. Lefrre J.J., Ravera N., Corbi C. et al. Infection with hepatitis G virus in
immunoglobulin recepients // Lancet. - 1997. - Vol. 349, 9046. - P. 206.
78. Vento S., Renzini C., Casali F. et al. Infection with hepatitis G virus in immunoglobulin
recepients // Lancet. 1997. Vol. 349, 9046. P. 206.
79. Ahsan N. Acute renal failure following immunoglobulin therapy // Am. J. Nephrol.
1996. Vol. 16, 6. P. 532-536.
80. Howse M., Bindoff L., Carmichael A. Facial vasculitis rash associated with intravenous
immunoglobulin // Brit. Med. J. - 1998. - Vol. 317, 7168. - P. 1291.
81. Dalakas M.C. High-dose intravenous immunoglobulin and serum viscosity: risk of
precipitating thromboembolic events // Neurology. - 1994. - Vol. 44, 2. - P. 223-226.
82. Ruch J., McMahon B., Ramsey G., Kwaan H.C. Catastrophic multiple organ ischemia
due to an anti-Pr cold agglutinin developing in a patient with mixed cryoglobulinemia after
treatment with rituximab // Am. J. Hematol. 2009. Vol. 84, 2. P. 120-122.
83. Voinov V.A. [Diabetes and efferent therapy] // Efferent Therapy (Rus). 2000. Vol. 6,
1. P. 18-23.