Hematuria was a high risk for renal progression and ESRD in immunoglobulin a nephropathy: a systematic review and meta-analysis

Figures & data

Figure 1. Flow chart of study selection from literature search.

Table 1. Primary characteristics of included studies.

Reference	Country	Design	Patients, no.	Age^a, yrs	Male, %	Protainuria^a, g/d	EGFR^a, ml/min per 1.73 m^2	Follow-up^a, yrs	ESRD, no.	Classification	Time point	Outcomes
De Menezes et al. [22]	Brazil	RCS	111	32	30.6	2.0	53	5.3	31	Hematuria	Biopsy	SCr doubling/ESRD
Bobart et al. [23]	USA	RCS	72	44.8	67.2	2.5	54.6	3.7	9	Hematuria	Biopsy	ESRD
Heybeli et al. [24]	Turkey	RCS	100	42.1	64	1.7	67	6.3	14	Macroscopic hematuria	Biopsy	SCr doubling/50% decline in eGFR/ESRD
Tanaka et al. [14]	Japan	RCS	88	33.9	38.6	0.3	89.4	NR	NR	Macroscopic hematuria	Biopsy	ESRD
Le et al. [25]	China	RCS	1155	34	49.7	0.9	89.7	7.9	155	Macroscopic hematuria	Before biopsy	ESRD
Bjørneklett et al. [27]	Norway	RCS	633	39	74	NR	67	10.3	146	Microscopic hematuria	Biopsy	ESRD
Lee et al. [26]	Korea	RCS	1364	33	50	1.3	67.6	8	277	Macroscopic hematuria	Biopsy	ESRD
Goto et al. [9]	Japan	PCS	2283	NR	48.7	NR	NR	7	207	Macroscopic and microscopic hematuria	Biopsy	ESRD
Espinosa et al. [28]	Spain	RCS	59	31.6	74.6	2.4	68.4	NR	11	Macroscopic hematuria	Biopsy	ESRD
Manno et al. [29]	Italy	RCS	437	31	67.7	0.7	NR	9	72	Microscopic hematuria	Onset	ESRD
Daniel et al. [30]	France	RCS	194	37.8	75.8	NR	NR	3.6	32	Hematuria	Biopsy	ESRD
Haas [31]	USA	RCS	109	38.4	73.4	2.9	NR	NR	NR	Macroscopic hematuria	Before biopsy	ESRD
Frimat et al. [32]	France	PCS	210	36.2	82.3	1.6	NR	5.6	33	Microscopic hematuria	Onset	ESRD

^aMedian or mean.

eGFR: estimated glomerular filtration rate; ESRD: end-stage renal disease; NR: not reported; PCS: prospective cohort study; RCS: retrospective cohort study; SCr: serum creatine level.

Figure 2. The meta-analysis on the association between initial hematuria and ESRD. CI: confidence interval; ESRD: end-stage renal disease; RR: relative risk.

Table 2. Subgroup analyses with regard to the association between various hematuria and end-stage renal disease.

Classification	Study no.	Patient no.	RR (95% CI)	p Value	I^2
Initial hematuria	7	3940	1.32 (0.87, 2.00)	.190	72%
hematuria	3	377	0.79 (0.44, 1.42)	.434	36.7%
Microscopic hematuria	4	3563	1.87 (1.40, 2.50)	<.001	23.7%
At biopsy	5	3293	1.21 (0.69, 2.12)	.503	79.1%
Disease onset	2	647	1.63 (0.90, 2.93)	.107	38.5%
Europe and America	6	1657	1.16 (0.78, 1.74)	.468	56.5%
Proteinuria > 1 g/d	3	393	1.01 (0.73, 1.39)	.962	0%
EGFR < 60 ml/min/1.73m^2	2	183	0.99 (0.70, 1.41)	.961	0%
Initial macroscopic hematuria	7	5158	0.68 (0.58, 0.79)	<.001	12.2%
At biopsy	5	3894	0.68 (0.57, 0.82)	<.001	23.2%
Before biopsy	2	1264	0.60 (0.41, 0.87)	.008	0%
Aisa	4	4890	0.59 (0.46, 0.76)	<.001	0%
Europe and USA	3	268	0.70 (0.56, 0.89)	.003	32.2%
Proteinuria > 1 g/d	5	3915	0.64 (0.52, 0.80)	<.001	39.5%
Proteinuria < 1 g/d	2	1243	0.67 (0.44, 1.00)	.052	0%
EGFR > 60 ml/min/1.73m^2	5	2766	0.73 (0.64, 0.83)	<.001	0%

CI: confidence interval; eGFR: estimated glomerular filtration rate; RR: risk ratio.

Figure 3. The meta-analysis on the association between initial macroscopic hematuria and ESRD. CI: confidence interval; ESRD: end-stage renal disease; RR: relative risk.

Table

Section/topic	Item No.	Checklist item	Page No.
Title
Title	1	Identify the report as a systematic review, meta-analysis, or both	1
Abstract
Structured summary	2	Provide a structured summary including, as applicable, background, objectives, data sources, study eligibility criteria, participants, interventions, study appraisal and synthesis methods, results, limitations, conclusions and implications of key findings, systematic review registration number	2
Introduction
Rationale	3	Describe the rationale for the review in the context of what is already known	3
Objectives	4	Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design	3
Methods
Protocol and registration	5	Indicate if a review protocol exists, if and where it can be accessed, and, if available, provide registration information including registration number	4
Eligibility criteria	6	Specify study characteristics (such as PICOS, length of follow-up) and report characteristics (such as years considered, language, publication status) used as criteria for eligibility, giving rationale	4
Information sources	7	Describe all information sources (such as databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched	4
Search	8	Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated	4
Study selection	9	State the process for selecting studies (that is, screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis)	5
Data collection process	10	Describe method of data extraction from reports (such as piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators	5,6
Data items	11	List and define all variables for which data were sought (such as PICOS, funding sources) and any assumptions and simplifications made	5,6
Risk of bias in individual studies	12	Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis	6
Summary measures	13	State the principal summary measures (such as risk ratio, difference in means)	6
Synthesis of results	14	Describe the methods of handling data and combining results of studies, if done, including measures of consistency (such as I^2) for each meta-analysis	6,7
Risk of bias across studies	15	Specify any assessment of risk of bias that may affect the cumulative evidence (such as publication bias, selective reporting within studies)	6,7
Additional analyses	16	Describe methods of additional analyses (such as sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified	7
Results
Study selection	17	Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram	7
Study characteristics	18	For each study, present characteristics for which data were extracted (such as study size, PICOS, follow-up period) and provide the citations	7
Risk of bias within studies	19	Present data on risk of bias of each study and, if available, any outcome-level assessment	8
Results of individual studies	20	For all outcomes considered (benefits or harms), present for each study (a) simple summary data for each intervention group and (b) effect estimates and confidence intervals, ideally with a forest plot	7
Synthesis of results	21	Present results of each meta-analysis done, including confidence intervals and measures of consistency	8-10
Risk of bias across studies	22	Present results of any assessment of risk of bias across studies	8-10
Additional analysis	23	Give results of additional analyses, if done (such as sensitivity or subgroup analyses, meta-regression)	8-10
Discussion
Summary of evidence	24	Summarise the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (such as health care providers, users, and policy makers)	10
Limitations	25	Discuss limitations at study and outcome level (such as risk of bias), and at review level (such as incomplete retrieval of identified research, reporting bias)	13
Conclusions	26	Provide a general interpretation of the results in the context of other evidence, and implications for future research	13
Funding
Funding	27	Describe sources of funding for the systematic review and other support (such as supply of data) and role of funders for the systematic review	14

Table

#12. #7 AND #11	3,241	14 May 2020
#11. #8 OR #9 OR #10	57,269	14 May 2020
#10. Haematuria	8,697	14 May 2020
#9. hematuria	55,747	14 May 2020
#8. 'hematuria'/exp	49,550	14 May 2020
#7. #1 OR #2 OR #3 OR #4 OR #5 OR #6	32,055	14 May 2020
#6. berger AND disease	13,767	14 May 2020
#5. iga AND type AND nephritis	425	14 May 2020
#4. immunoglobulin AND a AND nephropathy	16,671	14 May 2020
#3. iga AND nephropathy	10,193	14 May 2020
#2. iga AND glomerulonephritis	5,731	14 May 2020
#1. 'immunoglobulin a nephropathy'/exp	11,360	14 May 2020

Table

References	Representa- tiveness^a	Selection of non-exposed^b	Ascertainment of exposure^c	Incident disease^d	Comparabi-lity^e	Outcome assessment^f	Length of follow-up^g	Adequacy of follow up^h	Quality score
De Menezes 2020 [22]	B	A	A	B	B	B	A	D	6
Bobart 2019 [23]	A	A	A	B	B	B	B	C	5
Heybeli 2019 [24]	A	A	A	B	B	B	A	C	6
Tanaka 2015 [14]	B	A	A	B	A + B	B	B	D	6
Le 2014 [25]	A	A	A	B	B	B	A	D	6
Bjørneklett 2012 [27]	A	A	A	B	A + B	B	A	D	7
Lee 2012 [26]	A	A	A	B	B	B	A	B	7
Goto 2009 [9]	A	A	A	A	A + B	B	A	C	8
Espinosa 2009 [28]	A	A	A	B	B	B	B	D	5
Manno 2007 [29]	A	A	A	B	A + B	B	A	C	7
Daniel 2000 [30]	A	A	A	B	A + B	C	B	D	5
Haas 1997 [31]	A	A	A	B	B	B	B	C	5
Frimat 1997 [32]	A	A	A	A	B	A	A	C	7

^aA, truly representative; B, somewhat representative; C, selected group; D, no description of the derivation of the cohort.

^bA, drawn from the same community as the exposed; B, drawn from a diferent source; C, no description of the derivation of the non-exposed.

^cA, secure record; B, structured interview; C, written self-report; D no description.

^dDemonstration that the outcome of interest was not present at start of study: A yes, B no.

^eA, study controls for demographics/comorbidities; B, study controls for any additional factor; C not done.

^fA, independent or blind assessment; B, record linkage; C, self-report; D, no description.

^gLong enough for outcomes to occur? A, yes (≥ 5 yrs); B, no (< 5 yrs).

^hA, complete follow-up; B, subjects lost to follow-up was unlikely to introduce bias; C, follow-up rate 90% or lower; D no statement.

Table

Authors/Publication years	Study excluded, pooled RRs	Study excluded, 95% CI
Initial hematuria
De Menezes (2020)	1.42	0.90 to 2.25
Bobart (2019)	1.31	0.85 to 2.03
Bjørneklett (2012)	1.27	0.77 to 2.11
Goto (2009)	1.16	0.78 to 1.74
Manno (2007)	1.20	0.74 to 1.95
Daniel (2000)	1.54	1.06 to 2.22
Frimat (1997)	1.35	0.85 to 2.15
Initial macroscopic hematuria
Heybeli/2019	0.60	0.49 to 0.74
Tanaka/2015	0.69	0.60 to 0.80
Le/2014	0.70	0.60 to 0.81
Lee/2012	0.72	0.63 to 0.82
Goto/2009	0.73	0.64 to 0.82
Espinosa/2009	0.72	0.63 to 0.82
Haas/1997	0.70	0.61 to 0.80

CI, confidence interval; RR, relative risk.

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