М.Ю. Швецов, Чжэн Аньтай, Л.В.Козловская,НИО нефрологии НИЦ Первого МГМУ имени И.М.Сеченова. Кафедра внутренних болезней Факультета фундаментальной медицины МГУ имени М.В. Ломоносова
3. Альбуминурия
А0-1 А2 А3
Оптимальная
или
незначительно
повышенная
Высокая
Очень
высокая
<30 мг/г
<3 мг/ммоль
30-300 мг/г
3-30
мг/ммоль
>300 мг/г
>30
мг/ммоль
СКФ,мл/мин/1,73м2
С1
Высокая или
оптимальная
≥90 Низкий Умеренный Высокий
С2
Незначительно
снижена
60-89 Низкий Умеренный Высокий
С3а
Умеренно
снижена
45-59 Умеренный Высокий
Очень
высокий
С3б
Существенно
снижена
30-44 Высокий
Очень
высокий
Очень
высокий
С4 Резко снижена 15-29
Очень
высокий
Очень
высокий
Очень
высокий
С5 ТПН <15
Очень
высокий
Очень
высокий
Очень
высокий
Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical PracVce Guideline for the EvaluaVon and
Management of Chronic Kidney Disease. Kidney inter., Suppl. 2013; 3: 1–150.
4. Альбуминурия
А0-1 А2 А3
Оптимальная
или
незначительно
повышенная
Высокая
Очень
высокая
<30 мг/г
<3 мг/ммоль
30-300 мг/г
3-30
мг/ммоль
>300 мг/г
>30
мг/ммоль
СКФ,мл/мин/1,73м2
С1
Высокая или
оптимальная
≥90 Низкий Умеренный Высокий
С2
Незначительно
снижена
60-89 Низкий Умеренный Высокий
С3а
Умеренно
снижена
45-59 Умеренный Высокий
Очень
высокий
С3б
Существенно
снижена
30-44 Высокий
Очень
высокий
Очень
высокий
С4 Резко снижена 15-29
Очень
высокий
Очень
высокий
Очень
высокий
С5 ТПН <15
Очень
высокий
Очень
высокий
Очень
высокий
Дисфункция
Повреждение
Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical PracVce Guideline for the EvaluaVon and
Management of Chronic Kidney Disease. Kidney inter., Suppl. 2013; 3: 1–150.
5. Оценка функции
почек (СКФ)
• Цистатин C
• b-Trace protein
• β2-микроглобулин
Повреждение
тубулоинтерстиция
• NGAL
• KIM-1
• NAG
• L-FABP…
Повреждение
клубочков
• Подоцин
• Нефрин
• Подокаликсин…
Fassed RG, Venuthurupalli SK, Gobe GC et al. Biomarkers in chronic kidney disease: a review.
Kidney Int 2011;80:806–21.
• С-РБ, пентаксин-3, ФНО-α, ИЛ-18,
ТИМП-1, CD14…
Воспаление
• Фибриноген, ТФР-бета, Коллаген IV…
Фиброгенез
9. S. Kado et al. 1Diabetes Research and Clinical Practice 31 (1996) 103-108 105
NS
I P< 0.001 I
*7
1F-l .
z
B 20.
1
t
3 :15.
!
8 i .
5
g 10.
,x
x
i
.
2
'C 5. .
3 i-
P
Fig. 1. Urinary levels of type IV collagen in normal healthy
controls, subjects with non-insulin-dependent diabetes melli-
tus, and those with chronic glomerulonephritis. NIDDM, sub-
jects with non-insulin-dependent diabetes mellitus; CGN,
Table 1
Correlation coefficients for the relations between urinary type
IV collagen and other parameters in NIDDM subjects
Parameter Correlation coefficient P-vlaue
Age 0.23
Duration of diabetes 0.04
Plasma glucose 0.09
Fructosamine 0.14
H&c 0.21
Serum creatinine 0.05
Serum urea nitrogen 0.05
Serum total cholesterol 0.23
SBP 0.14
DBP 0.02
Urinary albumin 0.29
Urinary 0.54
G(1-microglobulin
Urinary NAG 0.27
Serum type IV 0.22
collagen
0.01
NS
NS
NS
0.02
NS
NS
0.01
NS
NS
0.001
0.0001
0.003
0.02
SBP, systolic blood pressure; DBP, diastolic blood pressure;
NAG, N-acetyl-p-D-glucosaminidase; NS, not significant.
bars.
were: 34.4 f 63.4, 6.5 + 7.7, and 280.8 +
392.7 mg/gCr, respectively. NIDDM subjects
were divided into five subgroups according to
their urinary level of albumin. As shown in
Fig. 2. Urinary levels of type IV collagen in normal healthy
controls, and NIDDM subjectswith various levels of albumin-
uria. UALB, urinary albumin; NIDDM, patients with non-in-
sulin-dependent diabetes mellitus.
Kado S, Aoki A, Wada S et al. Urinary type IV collagen as a marker for early diabeVc
nephropathy. Diabetes Res Clin Pract 1996;31:103–8.
10. Figure 1—Correlation analysis in study population of urinary type IV collagen (ng/mg creati-
nine) with A:C ratios (A: r ϭ 0.12; NS when outlier at A:C ratio of 3,080 is excluded; r ϭ 0.37, P ϭ
0.10 when outlier is included) and with RSC values (B: r ϭ Ϫ0.62; P Ͻ 0.001).
dy
4)
1 / креатинин сыв. Альбуминурия
Cohen MP, Lautenslager GT, Shearman CW. Increased collagen IV excreVon in diabetes.
A marker of compromised filtraVon funcVon. Diabetes Care 2001;24:914–8.
13. Оценка функции
почек (СКФ)
• Цистатин C
• b-Trace protein
• β2-микроглобулин
Повреждение
тубулоинтерстиция
• NGAL
• KIM-1
• NAG
• L-FABP
Повреждение
клубочков
• Подоцин
• Нефрин
• Подокаликсин
Fassed RG, Venuthurupalli SK, Gobe GC et al. Biomarkers in chronic kidney disease: a review.
Kidney Int 2011;80:806–21.
• С-РБ, MCP-1, пентаксин-3, ФНО-α, ИЛ-18,
ТИМП-1, CD14…
Воспаление
• Фибриноген, ТФР-бета, Коллаген IV…
Фиброгенез
14.
15. A.Bohle et al. Pathol Res Pract. 1990 Feb;186(1):135-44.
function of the kidney is impaired. These results also corroborate those of earlier
work by Spuhler and Zollinger4 , Risdon et and Schainuck et a1. 6 • Moderately
severe mesangioproliferative glomerulonephritis can be taken as an example. Here we
found a significant correlation between the degree of widening of the renal cortical
interstitium resulting from fibrotic processes and the serum creatinine level (Fig
1). As a result, the serum creatinine concentration in cases having the same degree
of severity of mesangioproliferative glomerulonephritis may be normal in some and
irreversibly elevated in others (Figs. 2a and b).
_ _ _
, n· II I
_ _ ,·o.ne
Fig. 1. Correlation
interstitium and
mesangioproliferative
interstitium
between the relative volume of the renal cortical
the serum creatinine concentration in
glomerulonephritis. N normal width of the
It remains within the normal range as long as the inflammatory process is confined to
the glomerulus. However, when the renal cortical interstitium is widened by an
accompanying inflammatory process leading to fibrosis and the tubules are atrophic,
the serum creatinine concentration becomes irreversibly elevated. What is true of
mesangioproliferative glomerulonephritis also applies to all the other well-defined
glomerulonephritides.
We have not, as yet, been able to detect any measurable decline in the glomerular
filtration rate as a result of glomerular disease alone. This can be illustrated with
the particularly impressive case of membranoproliferative glomerulonephritis type I
shown in Figs. 3a and b: the glomeruli exhibit double contouring of the basement
membrane, swelling of the endothelium and marked proliferation of the mesangial
cells. In spite of these changes, the patient's serum creatinine concentration was
0.8 mg!! and the creatinine clearance 120 ml/min - both within the normal range.
According to the results of our study, peri reticular renal amyloidosis, too, is
accompanied by irreversible elevation of the serum creatinine concentration only when
Креатинин
сыв., мг/дл
Отн.объем интерстиция
R=0,7242
Нормальный отн. объем интерстиция,
неизмененые канальцы.
Креатинин сыв. 0,8 мг/дл
Выраженный тубулоинтерстициальный
компонент. Креатинин сыв. 2,8 мг/дл
Отн.объем
31
There is also clear evidence in the case of diabetic glomerulosclerosis th
glomerular changes alone do not have a detrimental effect on the excretory f
Figs 2a and b. Moderately severe mesangioproliferative glomeruloneph
a) The tubules are unremarkable and the interstitium is of normal w
Serum creatinine concentration: 0.8 mg%. b) The interstitium is wide
fibrosed and inflamed and the tubules are atrophic. Serum creati
concentration: 2.8 mgt.
31
There is also clear evidence in the case of diabetic glomerulosclerosis tha
glomerular changes alone do not have a detrimental effect on the excretory fu
Figs 2a and b. Moderately severe mesangioproliferative glomerulonephr
a) The tubules are unremarkable and the interstitium is of normal wi
Serum creatinine concentration: 0.8 mg%. b) The interstitium is widen
fibrosed and inflamed and the tubules are atrophic. Serum creatin
concentration: 2.8 mgt.
. Section of the renal cortex in hypokalaemic nephropathy, showing
interstitial fibrosis and atrophy of the tubules. The glomeruli are
alinized, but the maximal urine osmolality is only 360 mosm; that is,
dney is unable to concentrate the urine, despite the fact that the
uli are preserved. PAS reaction.
be illustrated with two examples. Firstly, mesangioproliferative
ephritis (Fig. 8): for patients without tubulo-interstitial changes at the
biopsy, the lO-year kidney survival rate is 92%; if, on the other hand,
gns of tubulo-interstitial fibrosis in addition to the glomerular changes
of biopsy, this falls to 65%.
III
.0
i
!
..
1
"0
..0
It
LONG-TERM PROGNOSIS OF MESANGIOPROUFERATIVE GN
IN RELATION TO INTERSTITIAL FIBROSIS (n. 456 I
80
80
.0
20
0
Follow - up " ••r.1
NORMAL INTERSTITIUM
INTERSTITIAL FIBROS
( 23" I
10
Почечная выживаемость
Годы наблюдения
Норм. интерстиций
ТИФ
17. also confirm results published by Risdon et aI." and Schainuck et al.".
ndings, obtained by semiquantitative methods, have received virtually no
n.
also been able to demonstrate over the last few years that still more
s can be affected by tubulo-interstitial changes. In patients with
oproliferative glomerulonephritis whose maximum urine osmolality was measured
time of renal biopsy, we were able to demonstrate a significant negative
ion between the width of the renal cortical interstitium and the maximum
concentrating ability of the kidney. In other words, the concentrating
diminishes progressively as the renal cortical interstitium increases in
ig. 4). This correlation was also noted by both Risdon et al." and Schainuck
as a result of their semiquantitative investigations.
y
r'20 ..
10
200 400 600
n·89
r-O.81
2p·0.0001
800
x
1000
4. Correlation between the maximal urine osmolality and the relative
me of the cortical interstitium in cases of various glomerulopathies,
nly mesangioproliferative glomerulonephritis. A statistically
nificant negative correlation exists between these parameters; i.e., as
interstitium of the cortex increases in width, the maximal urine
olality decreases significantly.
y, correlations were also found between the urine osmolality and the cross-
l area of the epithelium of the proximal tubules and of the distal tubules,
A.Bohle et al. Pathol Res Pract. 1990 Feb;186(1):135-44.
Объем
интерстиция
Осмолярность мочи, мосмоль/л
R=0,81
33
CORRELATION BETWEEN OSMOLALITY OF THE URINE AND EPITHELIAL AREA OF T
PROXIMAL TUBULES RESP. EPITHEliAL AREA OF THE THICK SEGMENT OF LOOP OF HE
MEDULLA CORTEX
URINE THICK SEGMENT OF LOOP OF HENLE PROXIMAL TUBULES
OSMOL
(mosmol Il
1 : 9 • 1."'.
r ; 0,64
p : 0,0001
..:.
.'
....
. ..
.'
y : -;]23,6 • O,B
r = 0,7
p " 0.0001
63
800 1600
TUBULAR EPITHELIAL AREA wm")
Fig. 5. Correlation between the cross-sectional area o
the proximal tubules and of the ascending limb of H
maximal urine osmolality. It is seen that as the area
decreases, the maximal urine osmolality decreases signif
Площадь тубулярного эпителия, мкм2
Осмоляр-
ность мочи,
мосмоль/л
Прокс.канальцы Восх.сегм. п. Генле
20. 5 µm
2Cl
–
Cl–
Na+
3Na+
Ca2+
Mg2+
K+
Na+
K+
K+
2K+ROMK
UMOD
H2O
Luminal Basolateral
+ –
Cldns
NKCC2
CIC–Kb
Barttin
Na/K–
ATPase
Figure 1 |Uromodulin, a major secretory protein produced by the cells lining the thick ascending limb o
is exclusively produced by the cells lining the thick ascending limb (TAL), a tubular segment involved in NaCl r
cations (Ca2+
and Mg2+
), and urine concentration. Uromodulin is a glycosylphosphatidylinositol (GPI)-anchored
the apical membrane, cleaved by a protease, and assembled in the urine into polymers that form a gel-like
Devuyst O, Bochud M. Uromodulin, kidney func•on, cardiovascular
disease, and mortality. Kidney Int 2015;88:944–6.
21. a
23 31 148 198 287 334 585 640614
GPI
I II III D8C ZP_N ZP_C
b
TAL tubular
epithelial cell
Lumen
GPI anchoring
Protein folding
N-glycosylation
N-glycan
maturation
Polymerization
Urinary excretion
Proteolysis
gure 1 | Structure and maturation of uromodulin. (a) The predicted structure of uromodulin contains a leader peptide (predicted to be
eaved at residue 23), three epidermal growth factor (EGF)-like domains (EGF-II and EGF-III are calcium binding), a central domain of
nknown function (named D8C as it contains eight conserved cysteines), a zona pellucida (ZP) domain, and a glycosylphosphatidylinositol
GPI)-anchoring site (predicted at position 614). The seven N-glycosylation sites are indicated. The high-mannose chain on residue Asn 274 is
hown in red. (b) Model of uromodulin maturation, excretion, and polymerization. Uromodulin is synthesized in thick ascending limb (TAL)
bular epithelial cells. It is co-translationally inserted in the endoplasmic reticulum where GPI anchoring, formation of intramolecular
sulfide bonds, and N-glycosylation take place. In the Golgi, all glycan chains are modified, with the exception of the one on Asn 274 that
Rampoldi et al.: Uromodulin and chronic diseases of the kidney mini review
Rampoldi L, Scolari F, Amoroso A et al. The rediscovery of uromodulin (Tamm-
Horsfall protein): from tubulointersVVal nephropathy to chronic kidney disease.
Kidney Int 2011;80:338–47.
22. tly, renal cysts [5–7, 10]. More than 100 mutations in the
OD gene have been described so far; the majority of re-
ted UMOD mutations cluster in exons 4 and 5, resulting in
replacement of cysteine residues and leading to misfolding
tions affect biosynthesis of the
intracellular trafficking, ER stor
sion in the kidney and decreased
opposed to mice expressing m
U R E 1 : Structure of UMOD protein and summary of the published mutations associated with UADK. U
of the structure of the UMOD protein, showing a leader peptide, three epidermal growth factor EGF-like d
C, a ZP domain and a glycosylphosphatidylinositol GPI-anchoring site. Glycosylation sites are represented
Scolari F, Izzi C, Ghiggeri GM. Uromodulin: from monogenic to mulVfactorial
diseases. Nephrol Dial Transpl 2014;0:1–7.
23. Nomenclature and classification
With the discovery of multiple genes causing a similar syn-
drome, it became clear that the time-honoured FJHN was in
need of a more appropriate diagnostic term. Mutations in
& ADTKD-HNF1β
& ADTKD-NOS (not otherwise specified)
The subject has been well summarised in a recent commen-
tary [25].
Table 1 Nomenclature of uromodulin and its related mutations in the online database of inherited diseases (OMIM)
Name of disorder Abbreviation Mutant gene Cytogenetic location Phenotype Gene/locus
Hyperuricemic Nephropathy, Familial Juvenile, 1 HNFJ1 UMOD 16p12.3 162000 191845
Medullary cystic kidney disease type 2 MCKD2 UMOD 16p12.3 603860 191845
Glomerulocystic kidney disease GCKD UMOD 16p12.3 609886 191845
Hyperuricaemic nephropathy, Familial juvenile, 2 HNFJ2 REN 1q32.1 613092 179820
Renal tubular agenesis REN 1q32.1 267430 179820
Hyperuricaemic nephropathy, Familial juvenile, 3 HNFJ3 unknown 2p22.1-p21 614227 614227
Maturity onset diabetes of the young MODY HNF1b 17q12 125853 189907
Renal cysts and diabetes syndrome RCAD HNF1b 17q12 137920 189907
Medullary cystic kidney disease type 1 MCKD1 MUC1 1q22 174000 158340
Juvenile nephronophthisis type 1 NPHP1 NPHP1 2q13 256100 607100
Autosomal recessive polycystic kidney disease ARPKD FCYT 6p12.3-p12.2 263200 606702
UMOD, uromodulin; REN, renin; MUC1, mucin 1; NPHP1, nephronophthisis 1; FCYT, alternative name for PKHD1 (polycystic kidney and hepatic
disease 1 autosomal recessive)
Pediatr Nephrol, Feb. 2016. DOI 10.1007/s00467-015-3308-y
24. Nomenclature and classification
With the discovery of multiple genes causing a similar syn-
drome, it became clear that the time-honoured FJHN was in
need of a more appropriate diagnostic term. Mutations in
& ADTKD-HNF1β
& ADTKD-NOS (not otherwise specified)
The subject has been well summarised in a recent commen-
tary [25].
Table 1 Nomenclature of uromodulin and its related mutations in the online database of inherited diseases (OMIM)
Name of disorder Abbreviation Mutant gene Cytogenetic location Phenotype Gene/locus
Hyperuricemic Nephropathy, Familial Juvenile, 1 HNFJ1 UMOD 16p12.3 162000 191845
Medullary cystic kidney disease type 2 MCKD2 UMOD 16p12.3 603860 191845
Glomerulocystic kidney disease GCKD UMOD 16p12.3 609886 191845
Hyperuricaemic nephropathy, Familial juvenile, 2 HNFJ2 REN 1q32.1 613092 179820
Renal tubular agenesis REN 1q32.1 267430 179820
Hyperuricaemic nephropathy, Familial juvenile, 3 HNFJ3 unknown 2p22.1-p21 614227 614227
Maturity onset diabetes of the young MODY HNF1b 17q12 125853 189907
Renal cysts and diabetes syndrome RCAD HNF1b 17q12 137920 189907
Medullary cystic kidney disease type 1 MCKD1 MUC1 1q22 174000 158340
Juvenile nephronophthisis type 1 NPHP1 NPHP1 2q13 256100 607100
Autosomal recessive polycystic kidney disease ARPKD FCYT 6p12.3-p12.2 263200 606702
UMOD, uromodulin; REN, renin; MUC1, mucin 1; NPHP1, nephronophthisis 1; FCYT, alternative name for PKHD1 (polycystic kidney and hepatic
disease 1 autosomal recessive)
Pediatr Nephrol, Feb. 2016. DOI 10.1007/s00467-015-3308-y
• Гиперурикемическая нефропатия, семейная
ювенильная, 1
• Медуллярная кистозная болезнь почек, 2 тип
• Гломерулокистозная болезнь почек
25. F I G U R E 1 : UMOD regulates NKCC2 and ROMK function, presumably by modulating their turnover and NKC
(A) Normal condition with phosphorylation of NKCC2 (+). (B) In the case of UMOD reduced expression: sub-ap
and NKCC2 with reduced NKCC2 phosphorylation.
Zacchia M, Capasso G. The importance of uromodulin as regulator of salt reabsorpVon
along the thick ascending limb. Nephrol Dial Transplant 2015;30:158–60.
26. моче устанавливались с помощью стандартных
лабораторных автоанализаторов. Концентрации
Умо в сыворотке крови и моче измерялись иммуно-
ферментным способом с использованием наборов
Концен
ратно ассо
ной атроф
ТХБобрат
ной инфил
В свою оч
кровитакж
атрофии к
скулярног
Интересно
(по данным
свете поче
ТХБ оказы
пациентам
2). Скольк
концентра
поврежден
Доказат
связи межд
ви и моче
Рис. 1. Взаимосвязь между выраженностью атрофии каналь-
цев и концентрацией уромодулина в моче (коэффициент
А.В. Смирнов, М. Хасун, И.Г. Каюков и соавт., Нефрология. 2015. Том 19. No2.
27. А.В. Смирнов, М. Хасун, И.Г. Каюков и соавт., Нефрология. 2015. Том 19. No2.
6274. Нефрология. 2015. Том 19. №2.
ивые све-
рогресси-
т немало
ективную
ирования
жено, что
ела петли
[12]. Со-
почки от
подавле-
рецептор
ить вклад
необразо-
Умо, ока-
инфекций
лено, что
шающую
акта [16].
Умо обе-
системы
птивного
еханизма.
усилива-
Рис. 3. Уровень среднего систолического артериального дав-
ления в дневные часы в зависимости от выраженности атро-
фии канальцев и концентрации уромодулина в моче (UУмо).
Генле может приводить к развитию ОПП [12]. Со-
общалось также, что Умо предохраняет почки от
ишемической травмы за счет уменьшения подавле-
ния воспаления через влияние на TLR4-рецептор
[13]. Кроме того, дефекты Умо могут вносить вклад
в формирование нефрокальциноза и камнеобразо-
вание [2, 14]. Мыши, нокаутные по гену Умо, ока-
зались более подверженными к развитию инфекций
мочевых путей [15]. Было также выявлено, что
N-гликаны, переносимые Умо, играют решающую
роль в защите от поражений мочевого тракта [16].
M.D. Saemann и соавт. [17] показали, что Умо обе-
спечивает связь между активацией клеток системы
врожденного иммунитета и системой адаптивного
иммунитета за счет TLR4-зависимого механизма.
Сообщалось, что у Умо-нокаутных мышей усилива-
ется стресс-индуцированное мочеиспускание [18].
В свете представлений о нефропротекторной
роли Умо парадоксальными кажутся результаты
ряда недавних проспективных популяционно-
генетических исследований. Оказалось, что не-
которые распространенные варианты однону-
клеотидных полиморфизмов гена Умо (не путать
с мутациями гена Умо, вызывающими болезни
накопления уромодулина – авт.) четко ассоцииро-
ваны с более высокой почечной экскрецией ТХБ и
большей заболеваемостью и распространенностью
ХБП [19–22]. Правда, в популяции пациентов с
коронарной болезнью сердца было подтверждено,
что у носителей минорного аллеля (ТТ) варианта
однонуклеотидного полиморфизма rs12917707
действительно наблюдается меньшая концентрация
Умо в моче. Однако сами мочевые уровни ТХБ не
ассоциировались с заболеваемостью ХБП [23]. Ин-
тересно также, что у реципиентов почечного транс-
плантата, пересаженного от доноров-носителей
Рис. 3. Уровень среднего систолического артериального дав-
ления в дневные часы в зависимости от выраженности атро-
фии канальцев и концентрации уромодулина в моче (UУмо).
Рис. 4. Уровень среднего систолического артериального
давления в дневные часы в зависимости от выраженности
атрофии канальцев и концентрации уромодулина в сыворотке
крови (SУмо).
Концентрация уромодулина в моче
(UУмо).
Концентрация уромодулина в сыворотке
крови (SУмо).
28. B E D S I D E AN D B E N C H
live long enough develop
sease that requires dialysis
t to sustain life.
elucidating genetic variants
modify the risk of adult-
ecently published studies
ucleotide polymorphisms
OD gene promoter—the
sition –3,653 (rs12917707)
h a 20% reduction in CKD
inor C allele at position
) was associated with bet-
in both incident people
ntrols in the US5, whereas
ele at this site was associ-
d CKD risk in an Icelandic
minor G allele at position
26) was associated with
pertension and with renal
pean study7.
dings provide a new win-
ty to probe further into
f CKD, with UMOD as a
ould these minor genetic
nctionally altered proteins
iversal pathogenetic path-
e CKD, irrespective of the
—characterized as chronic
Loss of protective functions
Gain of damaging functions or mislocation
Basolateral
membrane
↑ Basolateral
expression
↓ Apical
membrane levels
Gel permeability
barrier
Protection
from damage?
Urinary protein
(UMOD)
Coreceptor
Lipid raft
GPI-anchored UMOD
Interstitial cell
recruitment
and activation
Interstitial deposition
Protein misfolding
Tubular
back-leak
Macrophage
Fibroblast
Dead
cell
ER
ER stress
Epithelial cell death
Permeability
barrier
dysfunction
Extracellular
matrix
Nephron
DCT
TAHL
Fibrosis CKD
Uromodulin
Cilia
Figure 1 UMOD, normal and genetically determined variants, may actively participate in the
pathogenesis of CKD. UMOD is normally expressed by epithelia of the TALH and the early distal tubule
(DCT). Loss of protective UMOD activities might impair tubular recovery after injury, alter tubular
transport function or enhance calcium crystal deposition. Gain of damaging functions or mislocation
MarinaCorral
Eddy AA. UMODulaVng renal fibrosis. Nat Publ Gr 2011;17:553–5.
Теряет свои защитные свойства
Проникает в интерстиций, индуцируя воспаление
29. 1758 Risch et al.: Serum uromodulin and kidney function
Figure 1 Relationship between serum uromodulin and (A) serum creatinine, (B) serum cystatin C, (C) blood urea nitrogen an
The relationship between the retention markers and serum uromodulin is of an inverse nature. The scatterplots suggest a hy
relationship between the different markers, indicating a more than proportional increase in uromodulin concentrations with
Risch L, Lhoda K, Meier D et al. The serum uromodulin level is associated with
kidney funcVon. Clin Chem Lab Med 2014;52:1755–61.