Visual Abstract

Introduction: Kidney biopsies (KBs) are performed in patients with type 2 diabetes (T2D) to diagnose non-diabetic or hypertensive kidney disease (NDHKD) potentially requiring specific management compared to diabetic and or hypertensive nephropathy (absence of NDHKD). Indications for KB are based on the presence of atypical features compared to the typical course of diabetic nephropathy. In this study, we assessed the association of different patterns of atypical features, or KB indications, with NDHKD. Methods: Native KBs performed in patients with T2D were analyzed. Data were collected from the patients’ records. KB indications were determined according to the presence of different atypical features considered sequentially: (1) presence of any feature suggesting NDHKD which is not among the following ones, (2) recent onset of nephrotic syndrome, (3) low or rapidly declining estimated glomerular filtration rate (eGFR), (4) rapid increase in proteinuria, (5) short duration of diabetes, (6) presence of hematuria, or (7) normal retinal examination. Results: Among the 463 KBs analyzed, NDHKD was diagnosed in 40% of the total population and 54, 40, 24, and 7% of the KBs performed for indications 1–4 respectively. Conversely, no patient who underwent KB for indications 5–7 displayed NDHKD. Logistic regression analyses identified eGFRCKD-EPI >15 mL/min/1.73 m2, urinary protein-to-Cr ratio <0.3 g/mmol, hematuria, HbA1c <7%, and diabetes duration <5 years as predictors of NDHKD, independently from the indication group. Conclusion: NDHKD is frequent in T2D. Despite the association of hematuria with NDHKD, our results suggest that presence of hematuria and absence of DR are insufficient to indicate KB in the absence of concurrent atypical features. Conversely, rapid progression of proteinuria and rapid deterioration of eGFR are major signals of NDHKD.

1.
NCD Risk Factor Collaboration (NCD-RisC)
.
Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants
.
Lancet
.
2016 Apr 19
;
387
(
10027
):
1513
30
. .
2.
Doshi
SM
,
Friedman
AN
.
Diagnosis and management of type 2 diabetic kidney disease
.
Clin J Am Soc Nephrol
.
2017 Aug 7
;
12
(
8
):
1366
. .
3.
Bermejo
S
,
García-Carro
C
,
Soler
MJ
.
Diabetes and renal disease: should we biopsy?
Nephrol Dial Transplant
.
2019 Dec
;
28
:
gfz248
.
4.
KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease
.
Am J Kidney Dis
.
2007 Feb
;
49
(
2 Suppl 2
):
S12
154
.
5.
Lee
YH
,
Kim
KP
,
Kim
YG
,
Moon
JY
,
Jung
SW
,
Park
E
, et al
Clinicopathological features of diabetic and nondiabetic renal diseases in type 2 diabetic patients with nephrotic-range proteinuria
.
Medicine
.
2017 Sep
;
96
(
36
):
e8047
. .
6.
Fiorentino
M
,
Bolignano
D
,
Tesar
V
,
Pisano
A
,
Biesen
WV
,
Tripepi
G
, et al
Renal biopsy in patients with diabetes: a pooled meta-analysis of 48 studies
.
Nephrol Dial Transplant
.
2017 Jan
;
32
(
1
):
97
110
. .
7.
Zhou
J
,
Chen
X
,
Xie
Y
,
Li
J
,
Yamanaka
N
,
Tong
X
.
A differential diagnostic model of diabetic nephropathy and non-diabetic renal diseases
.
Nephrol Dial Transplant
.
2008 Jun
;
23
(
6
):
1940
5
. .
8.
Bermejo
S
,
Soler
MJ
,
Gimeno
J
,
Barrios
C
,
Rodríguez
E
,
Mojal
S
, et al
Predictive factors for non-diabetic nephropathy in diabetic patients. The utility of renal biopsy
.
Nefrologia
.
2016 Sep–Oct
[cited 2017 Mar 11];
36
(
5
):
535
44
. Available from: http://www.sciencedirect.com/science/article/pii/S2013251416301250.
9.
Bermejo
S
,
González
E
,
López-Revuelta
K
,
Ibernon
M
,
López
D
,
Martín-Gómez
A
, et al
Risk factors for non-diabetic renal disease in diabetic patients
.
Clin Kidney J
.
2020 Jun
;
13
(
3
):
380
8
. .
10.
Chemouny
J
,
Sannier
A
,
Hanouna
G
,
Raimbourg
Q
,
Dupuis
E
,
Daugas
E
, et al
Résultats d'une enquête sur les indications de biopsie rénale chez les patients diabétiques protéinuriques au sein de la communauté néphrologique française
.
Néphrol Thér
.
2018 Sep
;
14
(
5
):
376
. .
11.
Liu
XM
,
Dong
ZY
,
Zhang
WG
,
Liu
MY
,
Zhou
JH
,
Wang
Q
, et al
Validation of the 2007 kidney disease outcomes quality initiative clinical practice guideline for the diagnosis of diabetic nephropathy and nondiabetic renal disease in Chinese patients
.
Diabetes Res Clin Pract
.
2019 Jan
;
147
:
81
6
. .
12.
Erdogmus
S
,
Kiremitci
S
,
Celebi
ZK
,
Akturk
S
,
Duman
N
,
Ates
K
, et al
Non-diabetic kidney disease in type 2 diabetic patients: prevalence, clinical predictors and outcomes
.
Kidney Blood Press Res
.
2017
;
42
(
5
):
886
93
. .
13.
Horvatic
I
,
Tisljar
M
,
Kacinari
P
,
Matesic
I
,
Bulimbasic
S
,
Galesic Ljubanovic
D
, et al
Non-diabetic renal disease in Croatian patients with type 2 diabetes mellitus
.
Diabetes Res Clin Pract
.
2014 Jun
;
104
(
3
):
443
50
. .
14.
Ghani
AA
,
Al Waheeb
S
,
Al Sahow
A
,
Hussain
N
.
Renal biopsy in patients with type 2 diabetes mellitus: indications and nature of the lesions
.
Ann Saudi Med
.
2009 Dec
;
29
(
6
):
450
3
. .
15.
Wong
TY
,
Choi
PC
,
Szeto
CC
,
To
KF
,
Tang
NL
,
Chan
AW
, et al
Renal outcome in type 2 diabetic patients with or without coexisting nondiabetic nephropathies
.
Diabetes Care
.
2002
;
25
(
5
):
900
5
. .
16.
Harada
K
,
Akai
Y
,
Sumida
K
,
Yoshikawa
M
,
Takahashi
H
,
Yamaguchi
Y
, et al
Significance of renal biopsy in patients with presumed diabetic nephropathy
.
J Diabetes Investig
.
2013 Jan 29
;
4
(
1
):
88
93
. .
17.
Sharma
SG
,
Bomback
AS
,
Radhakrishnan
J
,
Herlitz
LC
,
Stokes
MB
,
Markowitz
GS
, et al
The modern spectrum of renal biopsy findings in patients with diabetes
.
Clin J Am Soc Nephrol
.
2013 Oct 7
;
8
(
10
):
1718
24
. .
18.
Chong
YB
,
Keng
TC
,
Tan
LP
,
Ng
KP
,
Kong
WY
,
Wong
CM
, et al
Clinical predictors of non-diabetic renal disease and role of renal biopsy in diabetic patients with renal involvement: a single centre review
.
Ren Fail
.
2012
;
34
(
3
):
323
8
. .
19.
von Elm
E
,
Altman
DG
,
Egger
M
,
Pocock
SJ
,
Gøtzsche
PC
,
Vandenbroucke
JP
, et al
The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies
.
PLoS Med
.
2007 Oct 16
;
4
(
10
):
e296
. .
20.
Tervaert
TW
,
Mooyaart
AL
,
Amann
K
,
Cohen
AH
,
Cook
HT
,
Drachenberg
CB
, et al
Pathologic classification of diabetic nephropathy
.
J Am Soc Nephrol
.
2010 Apr
;
21
(
4
):
556
63
. .
21.
RStudio Team
.
RStudio: integrated development environment for R [Internet]
.
Boston, MA
:
RStudio, Inc.
;
2016
. Available from: http://www.rstudio.com/.
22.
R Core Team
.
R: a language and environment for statistical computing [Internet]
.
Vienna, Austria
:
R Foundation for Statistical Computing
;
2017
. Available from: https://www.R-project.org/.
23.
Zhang
PP
,
Ge
YC
,
Li
SJ
,
Xie
HL
,
Li
LS
,
Liu
ZH
.
Renal biopsy in type 2 diabetes: timing of complications and evaluating of safety in Chinese patients
.
Nephrology
.
2011 Jan
;
16
(
1
):
100
5
. .
24.
Mami
I
,
Harzallah
A
,
Kaaroud
H
,
Aoudia
R
,
Hamida
FB
,
Goucha
R
, et al
Nondiabetic renal disease in patients with type 2 diabetes
.
Saudi J Kidney Dis Transpl
.
2017 Jul–Aug
;
28
(
4
):
842
50
.
25.
Liu
D
,
Huang
T
,
Chen
N
,
Xu
G
,
Zhang
P
,
Luo
Y
, et al
The modern spectrum of biopsy-proven renal disease in Chinese diabetic patients: a retrospective descriptive study
.
PeerJ
.
2018
;
6
:
e4522
. .
26.
Dong
Z
,
Wang
Y
,
Qiu
Q
,
Zhang
X
,
Zhang
L
,
Wu
J
, et al
Clinical predictors differentiating non-diabetic renal diseases from diabetic nephropathy in a large population of type 2 diabetes patients
.
Diabetes Res Clin Pract
.
2016 Nov
;
121
:
112
8
. .
27.
Lin
YL
,
Peng
SJ
,
Ferng
SH
,
Tzen
CY
,
Yang
CS
.
Clinical indicators which necessitate renal biopsy in type 2 diabetes mellitus patients with renal disease
.
Int J Clin Pract
.
2009 Aug
;
63
(
8
):
1167
76
. .
28.
Lee
EY
,
Chung
CH
,
Choi
SO
.
Non-diabetic renal disease in patients with non-insulin dependent diabetes mellitus
.
Yonsei Med J
.
1999 Aug
;
40
(
4
):
321
6
. .
29.
Tone
A
,
Shikata
K
,
Matsuda
M
,
Usui
H
,
Okada
S
,
Ogawa
D
, et al
Clinical features of non-diabetic renal diseases in patients with type 2 diabetes
.
Diabetes Res Clin Pract
.
2005 Sep
;
69
(
3
):
237
42
. .
30.
Haider
DG
,
Peric
S
,
Friedl
A
,
Fuhrmann
V
,
Wolzt
M
,
Hörl
WH
, et al
Kidney biopsy in patients with diabetes mellitus
.
Clin Nephrol
.
2011 Sep
;
76
(
3
):
180
5
. .
31.
Soni
SS
,
Gowrishankar
S
,
Kishan
AG
,
Raman
A
.
Non diabetic renal disease in type 2 diabetes mellitus
.
Nephrology
.
2006 Dec
;
11
(
6
):
533
7
. .
32.
Wilfred
DC
,
Mysorekar
VV
,
Venkataramana
RS
,
Eshwarappa
M
,
Subramanyan
R
.
Nondiabetic renal disease in type 2 diabetes mellitus patients: a Clinicopathological Study
.
J Lab Physicians
.
2013 Jul
;
5
(
2
):
94
9
. .
33.
Bi
H
,
Chen
N
,
Ling
G
,
Yuan
S
,
Huang
G
,
Liu
R
.
Nondiabetic renal disease in type 2 diabetic patients: a review of our experience in 220 cases
.
Ren Fail
.
2011
;
33
(
1
):
26
30
. .
34.
Wągrowska-Danilewicz
M
,
Danilewicz
M
.
Spectrum of biopsy-proven renal diseases in patients with type 2 diabetes mellitus. A single center study
.
Pol J Pathol
.
2015 Dec
;
66
(
4
):
361
7
.
35.
Liu
MY
,
Chen
XM
,
Sun
XF
,
Zhou
JH
,
Zhang
XG
,
Zhu
HY
, et al
Validation of a differential diagnostic model of diabetic nephropathy and non-diabetic renal diseases and the establishment of a new diagnostic model
.
J Diabetes
.
2014
;
6
(
6
):
519
26
. .
36.
Oh
SW
,
Kim
S
,
Na
KY
,
Chae
DW
,
Kim
S
,
Jin
DC
, et al
Clinical implications of pathologic diagnosis and classification for diabetic nephropathy
.
Diabetes Res Clin Pract
.
2012 Sep
;
97
(
3
):
418
24
. .
37.
Chang
TI
,
Park
JT
,
Kim
JK
,
Kim
SJ
,
Oh
HJ
,
Yoo
DE
, et al
Renal outcomes in patients with type 2 diabetes with or without coexisting non-diabetic renal disease
.
Diabetes Res Clin Pract
.
2011 May
;
92
(
2
):
198
204
. .
38.
Byun
JM
,
Lee
CH
,
Lee
SR
,
Moon
JY
,
Lee
SH
,
Lee
TW
, et al
Renal outcomes and clinical course of nondiabetic renal diseases in patients with type 2 diabetes
.
Korean J Intern Med
.
2013 Sep
;
28
(
5
):
565
72
. .
39.
Kritmetapak
K
,
Anutrakulchai
S
,
Pongchaiyakul
C
,
Puapairoj
A
.
Clinical and pathological characteristics of non-diabetic renal disease in type 2 diabetes patients
.
Clin Kidney J
.
2018 Jun 1
;
11
(
3
):
342
7
. .
40.
Suzuki
D
,
Takano
H
,
Toyoda
M
,
Umezono
T
,
Uehara
G
,
Sakai
T
, et al
Evaluation of renal biopsy samples of patients with diabetic nephropathy
.
Intern Med
.
2001 Nov
;
40
(
11
):
1077
84
. .
41.
Mak
SK
,
Gwi
E
,
Chan
KW
,
Wong
PN
,
Lo
KY
,
Lee
KF
, et al
Clinical predictors of non-diabetic renal disease in patients with non-insulin dependent diabetes mellitus
.
Nephrol Dial Transplant
.
1997 Dec
;
12
(
12
):
2588
91
. .
42.
Soleymanian
T
,
Hamid
G
,
Arefi
M
,
Najafi
I
,
Ganji
MR
,
Amini
M
, et al
Non-diabetic renal disease with or without diabetic nephropathy in type 2 diabetes: clinical predictors and outcome
.
Ren Fail
.
2015 May
;
37
(
4
):
572
5
. .
43.
Pallayova
M
,
Mohammed
A
,
Langman
G
,
Taheri
S
,
Dasgupta
I
.
Predicting non-diabetic renal disease in type 2 diabetic adults: the value of glycated hemoglobin
.
J Diabetes Complicat
.
2015 Jul
;
29
(
5
):
718
23
. .
44.
Pham
TT
,
Sim
JJ
,
Kujubu
DA
,
Liu
IL
,
Kumar
VA
.
Prevalence of nondiabetic renal disease in diabetic patients
.
Am J Nephrol
.
2007
;
27
(
3
):
322
8
. .
45.
Fioretto
P
,
Mauer
M
,
Brocco
E
,
Velussi
M
,
Frigato
F
,
Muollo
B
, et al
Patterns of renal injury in NIDDM patients with microalbuminuria
.
Diabetologia
.
1996 Dec
;
39
(
12
):
1569
76
. .
46.
World Health Organization
.
World report on vision
. In:
World report on vision
.
2019
.
47.
Palsson
R
,
Short
SAP
,
Kibbelaar
ZA
,
Amodu
A
,
Stillman
IE
,
Rennke
HG
, et al
Bleeding Complications After Percutaneous Native Kidney Biopsy: Results from the Boston Kidney Biopsy Cohort
.
Kidney Int Rep
.
2020 Mar 4
[cited 2020 Jan 30];
5
(
4
):
511
8
. Available from: .
48.
Corapi
KM
,
Chen
JL
,
Balk
EM
,
Gordon
CE
.
Bleeding complications of native kidney biopsy: a systematic review and meta-analysis
.
Am J Kidney Dis
.
2012 Jul
;
60
(
1
):
62
73
. .
49.
Poggio
ED
,
McClelland
RL
,
Blank
KN
,
Hansen
S
,
Bansal
S
,
Bomback
AS
, et al
Systematic review and meta-analysis of native kidney biopsy complications
.
Clin J Am Soc Nephrol
.
2020 Oct 15
;
15
(
11
):
1595
. .
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