Significance of intrarenal vascular lesions in Ig A nephropathy prognosis

doi:10.21203/rs.3.rs-4836375/v1

Download PDF

Research Article

Significance of intrarenal vascular lesions in Ig A nephropathy prognosis

https://doi.org/10.21203/rs.3.rs-4836375/v1

This work is licensed under a CC BY 4.0 License

Journal Publication

published 16 Oct, 2024

Read the published version in BMC Nephrology →

You are reading this latest preprint version

Background

Immunoglobulin A (IgA) nephropathy is the predominant primary glomerulonephritis globally and remains a subject of active research with a focus on understanding its course and prognosis. Although vascular lesions are associated with IgAN, the current histopathological grading systems do not consider intrarenal vascular lesions when predicting patient prognosis. Therefore, this retrospective study, conducted at Kyungpook National University Hospital between October 2016 and December 2021, aimed to elucidate the significance of intrarenal vascular lesions in IgAN by comparing the clinical data of patients with and without such lesions.

Methods

Data of patients with biopsy-confirmed primary IgAN between October 2016 and June 2021 at Kyungpook National University Hospital (Daegu, South Korea) were collected, and their medical records were reviewed. All slides from these 138 cases were independently pathologically reviewed by two nephropathologists (Y. J. K. and M. S. K.) using light microscope. The vascular lesions included in this study were fibrous intimal thickening, arteriolar wall thickening, and arteriolar hyalinosis. All cases were reviewed according to the Oxford Classification of IgA Nephropathy (2016) and Haas classification.

Results

Of the 138 patients, 88 exhibited at least one intrarenal vascular lesion. Patients with arteriolar wall thickening demonstrated a reduced estimated glomerular filtration rate (eGFR), elevated serum creatinine level and urine protein-to-creatinine ratio, an increased proportion of global glomerulosclerosis, and a higher histologic grade of interstitial fibrosis and tubular atrophy at the time of biopsy.

Conclusion

Arteriolar wall thickening in IgAN are associated with reduced eGFR and global glomerulosclerosis. Moreover, reduced eGFR and global glomerulosclerosis are correlated with the progression to end-stage renal disease. Although the direct correlation between vascular lesions and end-stage renal disease is not entirely clear, a marginally significant association (log-rank test, p = 0.06) was observed with arterial wall thickening. This study suggests the potential importance of vascular lesions in the prognosis of IgAN, encouraging further investigation using larger cohort studies to establish a clearer association.

Immunoglobulin A nephropathy

prognosis

intrarenal vascular lesion

glomerular filtration rate

Oxford

Haas

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide [1]. Research on the course and prognosis of the disease is ongoing, and patient prognosis is currently predicted through histopathological grading. The Oxford and Haas classifications are the representative grading systems. The Oxford classification evaluates and grades biopsy specimens based on the following five categories: mesangial hypercellularity (M), segmental sclerosis (S), interstitial fibrosis/tubular atrophy (T), and crescents (C) [2]. These parameters are associated with a reduced estimated glomerular filtration rate (eGFR) or progression to end-stage renal disease. The Haas classification classifies specimens into five grades according to the ratio of glomerular sclerosis to glomerular hypercellularity (classes I to V) [3]. As the proportion of glomeruli with sclerosis or hypercellularity increases, patients tend towards end-stage renal disease. In one study, intrarenal arterial-arteriolar lesions were more frequently associated with IgAN than with non-IgA nephropathy [4]. In this study, the prevalence of intrarenal small artery and arteriolar lesions was 54.6% in patients with IgAN and 26.6% in patients without IgAN (p < 0.01). However, the Oxford and Haas classifications do not consider intrarenal vascular lesions. Therefore, this study aimed to analyze these differences by comparing clinical data between patients with IgAN with intrarenal vascular lesions and patients with IgAN without intrarenal vascular lesions. We ultimately aimed to determine whether vascular lesions can be added to these classification methods.

Patients

This study was approved by the Institutional Review Board (IRB) of Kyungpook National University Hospital, Daegu, Korea (IRB FILE No. KNUH 2023-12-017, 8 January 2024). As the study was retrospective, the IRB waived the need for written informed consent. Data of patients with biopsy-confirmed primary IgAN between October 2016 and June 2021 at Kyungpook National University Hospital (Daegu, South Korea) were collected, and their medical records were reviewed. Patients older than 18 years and those with more than seven glomeruli on biopsy were included. Of the 166 patients, 138 were included in the study. At the time of biopsy, we collected data, including age, sex, past medical history, initial blood pressure, CKD-EPI eGFR [5], serum creatinine, serum blood urea nitrogen (BUN), urine protein-to-creatinine ratio (UPCR), serum albumin, hemoglobin, platelet count, serum uric acid, and total cholesterol levels from electronic medical records.

Histological evaluation

All slides from the 138 cases were independently pathologically reviewed by two nephropathologists (Y. J. K. and M. S. K.) who were blinded to the patient information. Any discrepancies in the pathological diagnosis between the pathologists were resolved through re-evaluation of the cases until consensus. The vascular lesions included in this study were fibrous intimal thickening (Fig. 1a), arteriolar wall thickening (Fig. 1b), and arteriolar hyalinosis (Fig. 1c). No cases with arteriolar fibrinoid necrosis, arteriolar thrombi, subintimal myxoid changes, or arteriolar onion skin changes were observed. Vascular lesions were scored using a two-tier system: no or mild change and moderate to severe change. Moderate to severe changes were considered positive, whereas no or mild changes were considered negative. All cases were reviewed according to the Oxford Classification of IgA Nephropathy 2016 and the Haas classification.

Outcome

Of the initial 138 patients, 35 were lost after follow-up, leaving 103 patients included in the survival analysis. The median follow-up time was 1442 days (range: 253–2529 days). Survival time was defined as the duration from the date of kidney biopsy until the date of the last follow-up or the occurrence of end-stage renal disease (eGFR < 15 mL/min/1.73 m²) requiring kidney replacement.

Statistical analysis

All analyses were conducted using R version 4.3.2, incorporating the "survival" and "Hmisc" packages from the R Foundation for Statistical Computing (Auckland, New Zealand). A p-value of p < 0.05 was considered statistically significant. Clinicopathological differences between the vascular lesion-positive and vascular lesion-negative groups were assessed using Fisher’s exact test and a two-sample t-test (Tables 1, 2, and 3). Survival analysis was performed using the log-rank test, Kaplan–Meier method (Fig. 2), and univariate and multivariate Cox proportional hazards models (Tables 4 and 5). The results were expressed as hazard ratios (HR) with 95% confidence intervals (CI).

The cohort comprised 70 male and 68 female patients, with a male-to-female ratio of 1:0.97. The mean age was 41.1 years (range, 18–74 years). The mean systolic blood pressure was 126.6 mmHg, and 50 patients (36.2%) had a history of hypertension. The distributions across the Haas classification classes I, II, III, IV, and V were 30.4%, 21.7%, 35.5%, 6.5%, and 5.8%, respectively. The mean eGFR 79.8 ml/min per body surface area (BSA), and the mean UPCR was 1.6 mg/g.

Clinical and pathologic features related to arteriolar wall thickening

Clinical and pathologic features related to arteriolar wall thickening are summarized in Table 1. Old age, a history of hypertension, high diastolic blood pressure, low eGFR, high UPCR, high serum creatinine, low albumin, high total cholesterol, and use of renin-angiotensin-aldosterone system (RAAS) blockers were associated with arteriolar wall thickening. In the Oxford classification, high S scores and T scores were associated with arteriolar wall thickening. Moreover, global glomerulosclerosis, high interstitial fibrosis and tubular atrophy (IFTA) grade, high inflammatory IFTA grade, and high total inflammation score were also associated with arteriolar wall thickening.

Table 1

Clinicopathological characteristics according to arteriolar wall thickening
	Arteriolar wall thickening (+)		Arteriolar wall thickening (-)
	(n = 76)		(n = 62)
Clinical Information
Gender (%)
Male		37(48.7)	33(53.2)		0.6
Female		39(51.3)	29(46.8)
Age (mean)		19–74 (46)	18–74 (35)		0.0000065*
Hypertension (%)		34(44.7)	16(25.8)		0.03*
DM (%)		5(6.6)	0(0)		0.06
Systolic BP, mm Hg (mean)		98–210 (128)	78–172 (124.8)		0.28
Diastolic BP, mm Hg (mean)		46–120 (76.7)	46–90 (72.1)		0.03*
eGFR, ml/min/BSA (mean)		9-128 (65.7)	15–155 (97.2)	0.00000005*
UPCR, mg/g (mean)		0.09–13.12 (2.17)	0.05–5.58 (1.07)		0.0009*
BUN, mg/dL (mean)		6-64.1 (20.1)	5.8–96 (16.6)		0.08
Scr, µmol/L (mean)		0.5–5.12 (1.4)	0.49–5.49 (1.0)		0.004*
Uric acid, µmol/L (mean)		3.1–11.4 (6.8)	3.5–11.3 (6.2)		0.055
Hemoglobin, g/L (mean)		8.4–17.1 (13.1)	4–19 (13.7)		0.1
Platelet count, ×109 /L (mean)		24–603 (254.6)	157–463 (265.6)		0.44
Albumin, g/L (mean)		1.9–5.1 (4.1)	2.7–5.4 (4.4)		0.003*
Total cholesterol, mmol/L (mean)		120–360 (207)	101–243 (171)		0.000005*
Medications
RAAS blockers (%)		47(61.8)	15(24.2)		0.00001*
Steroids and other immunosuppressants (%)		1(1.3)	1(1.6)		1
Oxford classification score
M0/1(%)		70(92.1)/6(7.9)	56(90.3)/6(9.3)		0.77
E0/1(%)		61(80.3)/15(19.7)	56(90.3)/6(9.7)		0.15
S0/1(%)		24(31.6)/52(68.4)	31(50)/31(50)		0.036*
T0/1/2(%)		35(46.1)/19(25)/22(28.9)	56(90.3)/4(6.5)/2(3.2)		0.00000007*
C0/C1/C2(%)		51(67.1)/23(30.3)/2(2.6)	42(67.7)/20(32.3)/0(0)		0.63
Pathological Features
Global glomerulosclerosis, % (mean)		0-96.3 (28.2)	0-63.6 (9.9)		0.0000009*
Haas I/II/III/IV/V (%)		17(22.4)/16(21.1)/28(36.8)/7(9.2)/8(10.5)	25(40.3)/14(22.6)/21(33.9)/2(3.2)/0(0)		0.01
IFTA 0/1/2/3(%)		14(18.4)/23(30.3)/18(23.7)/21(27.6)	39(62.9)/15(24.2)/5(8.1)/3(4.8)		0.0000001*
I IFTA 0/1/2/3(%)		17(22.4)/23(30.3)/24(31.6)/12(15.8)	41(66.1)/15(24.2)/3(4.8)/3(4.8)		0.0000002*
Ti 0/1/2/3(%)		18(23.7)/32(42.1)/11(14.5)/15(19.7)	42(67.7)/16(25.8)/2(3.2)/2(3.2)		0.0000006*

BP, blood pressure; eGFR, estimated glomerular filtration rate; BSA, body surface area; UPCR, urine protein-to-creatinine ratio; BUN, blood urea nitrogen; Scr, serum creatinine; RAAS renin-angiotensin-aldosterone system; IFTA, interstitial fibrosis and tubular atrophy. I IFTA, inflammatory IFTA; Oxford classification: M, mesangial hypercellularity; S, segmental sclerosis; T, interstitial fibrosis/tubular atrophy; C, and crescents.

Clinical and pathological features related to fibrous intimal thickening

The clinical and pathological features related to fibrous intimal thickening are summarized in (Table 2). Five people were excluded because of the absence of available vessels. Similarly, old age, low eGFR, high UPCR, low albumin, and high total cholesterol were related to fibrous intimal thickening. In the Oxford classification, a high T-score was observed. Moreover, global glomerulosclerosis, high IFTA grade, and total inflammation score were related to fibrous intimal thickening.

Table 2

Clinicopathological characteristics according to fibrous intimal thickening
	Intimal thickening (+)	Intimal thickening (-)	p-value
	(n = 47)	(n = 86)
Clinical Information
Gender (%)
Male	21(44.7)	47(54.7)	0.28
Female	26(55.3)	39(45.3)
Age (mean)	24–74 (49)	18–73 (37)	0.000004*
Hypertension (%)	21(44.7)	27(31.4)	0.14
DM (%)	1(2.1)	3(3.5)	1
Systolic BP, mm Hg (mean)	100–210 (130.1)	78–172 (125.2)	0.11
Diastolic BP, mm Hg (mean)	55–110 (77.1)	46–120 (73.7)	0.12
eGFR, ml/min/BSA (mean)	9-120 (64.6)	9-141 (88)	0.0002*
UPCR, mg/g (mean)	0.2–8.18 (2.19)	0.05–9.81 (1.29)	0.003*
BUN, mg/dL (mean)	10.3–64.1 (20.4)	6–96 (17.5)	0.2
Scr, µmol/L (mean)	0.5–4.92 (1.37)	0.55–5.49 (1.18)	0.2
Uric acid, µmol/L (mean)	4.4–11.4 (7)	3.1–11.3 (6.3)	0.06
Hemoglobin, g/L (mean)	8.7–17.1 (12.9)	4–19 (13.6)	0.07
Platelet count, ×109 /L (mean)	149–603 (273.2)	24–464 (250.3)	0.13
Albumin, g/L (mean)	2.1-5 (4)	2.7–5.4 (4.3)	0.006*
Total cholesterol, mmol/L (mean)	138–360 (207)	101–328 (182)	0.003*
Medications
RAAS blockers (%)	24(51.1)	38(44.2)	0.47
Steroids and immunosuppressants (%)	1(2.1)	1(1.2)	1
Oxford classification score
M0/1(%)	42(89.4)/5(10.6)	80(93)/6(7)	0.52
E0/1(%)	40(85.1)/7(14.9)	73(84.9)/13(15.1)	1
S0/1(%)	16(34)/31(66)	36(41.9)/50(58.1)	0.46
T0/1/2(%)	22(46.8)/11(23.4)/14(29.8)	67(77.9)/10(11.6)/9(10.5)	0.001*
C0/C1/C2(%)	29(61.7)/16(34)/2(4.3)	59(68.6)/27(31.4)/0(0)	0.17
Pathological Features
Global glomerulosclerosis, % (mean)	0-96.3 (26.3)	0–90 (16.2)	0.01*
Haas I/II/III/IV/V(%)	10(21.3)/12(25.5)/18(38.3)/3(6.4)/4(8.5)	30(34.9)/16(18.6)/31(36)/5(5.8)/4(4.7)	0.47
IFTA 0/1/2/3(%)	8(17)/15(31.9)/9(19.1)/15(31.9)	44(51.2)/22(25.6)/12(14)/8(9.3)	0.0002*
I IFTA 0/1/2/3(%)	13(27.7)/16(34)/10(21.3)/8(17)	43(50)/21(24.4)/15(17.4)/7(8.1)	0.066
Ti 0/1/2/3(%)	13(27.7)/17(36.2)/6(12.7)/11(23.4)	45(52.3)/30(34.9)/5(5.8)/6(7)	0.006*

Clinical and pathological features according to any vascular lesions

The clinical and pathological features according to any vascular lesions are summarized in Table 3. If the specimen exhibited at least one vascular lesion (arteriolar wall thickening, arteriolar hyalinosis, or fibrous intimal thickening), it was categorized as a vascular lesion (+). In the cohort, 88 specimens had vascular lesions and 50 had no vascular lesions. The vascular lesion (+) group was associated with old age, a history of hypertension, high diastolic blood pressure, low eGFR, high UPCR, high BUN, high serum creatinine, high uric acid, low albumin, high total cholesterol, and the use of renin-angiotensin-aldosterone system (RAAS) blockers. Specimens with vascular lesions had a high T-score in the Oxford classification. Moreover, global glomerulosclerosis, high IFTA grade, high inflammatory IFTA grade, and high total inflammation score were associated with vascular lesions.

Table 3

Clinicopathologic characteristics according to vascular lesions
	Vascular Lesions (+)	Vascular Lesions (-)	p-value
	(n = 88)	(n = 50)
Clinical Information
Gender (%)
Male	42(47.7)	28(56)	0.38
Female	46(52.3)	22(44)
Age (mean)	19–74 (46)	18–73 (32.5)	0.00000005*
Hypertension (%)	40(45.5)	10(20)	0.003*
DM (%)	5(5.7)	0(0)	0.16
Systolic BP, mm Hg (mean)	98–210 (127.8)	78–172 (124.5)	0.28
Diastolic BP, mm Hg (mean)	46–120 (76.4)	46–90 (71.6)	0.02*
eGFR, ml/min/BSA (mean)	9-135 (66.8)	15–155 (102.8)	0.000000001*
UPCR, mg/g (mean)	0.09–13.12 (2.0)	0.05–5.58 (1.0)	0.004*
BUN, mg/dL (mean)	6–96 (20.7)	5.8–62.3 (14.8)	0.005*
Scr, µmol/L (mean)	0.5–5.12 (1.39)	0.49–5.49 (1)	0.01*
Uric acid, µmol/L (mean)	3.1–11.4 (6.9)	3.5–11.3 (6)	0.009*
Hemoglobin, g/L (mean)	8.4–17.1 (13.2)	4–19 (13.7)	0.12
Platelet count, ×109 /L (mean)	24–603 (257.7)	157–462 (262.8)	0.7
Albumin, g/L (mean)	1.9–5.1 (4.1)	2.7–5.4 (4.4)	0.008*
Total cholesterol, mmol/L (mean)	101–360 (202.4)	102–243 (170.1)	0.00009*
Medications
RAAS blockers (%)	48(54.5)	14(28)	0.004*
Steroids and immunosuppressants (%)	2(2.3)	0(0)	0.5
Oxford classification score
M0/1(%)	80(90.9)/8(9.1)	46(92)/4(8)	1
E0/1(%)	73(83)/15(17)	44(88)/6(12)	0.47
S0/1(%)	31(35.2)/57(64.8)	24(48)/26(52)	0.15
T0/1/2(%)	44(50)/21(23.9)/23(26.1)	47(94)/2(4)/1(2)	0.0000002*
C0/C1/C2(%)	60(68.2)/26(29.5)/2(2.3)	33(66)/17(34)/0(0)	0.62
Pathological Features
Global glomerulosclerosis, % (mean)	0-96.3 (26.8)	0-51.9 (8)	0.000001*
Haas I/II/III/IV/V (%)	21(23.9)/21(23.9)/31(35.2)/7(8)/8(9)	21(42)/9(18)/18(36)/2(4)/0(0)	0.049
IFTA 0/1/2/3(%)	17(19.3)/29(33)/19(21.6)/23(26.1)	36(72)/9(18)/4(8)/1(2)	0.000000004*
I IFTA 0/1/2/3(%)	22(25)/28(31.8)/24(27.3)/14(15.9)	36(72)/10(20)/3(6)/1(2)	0.0000004*
Ti 0/1/2/3(%)	22(25)/38(43.2)/11(12.5)/17(19.3)	38(76)/10(20)/2(4)/0(0)	0.00000001*

Vascular lesions and prognosis.

Among the 138 enrolled patients, 103 patients had follow-up data (mean follow-up date: 1404.9 days), and during that period, nine patients reached the endpoint (the occurrence of end-stage renal disease, eGFR < 15 mL/min/1.73 m², requiring kidney replacement). The univariate Cox regression analysis showed that global glomerulosclerosis, low eGFR, high BUN, high serum creatinine, and low albumin were associated with eventual progression to end-stage renal disease (Table 4). Multivariate Cox hazard analysis also showed that global glomerulosclerosis and high serum creatinine levels were associated with progression to end-stage renal disease after adjustment for any vascular lesions, arteriolar wall thickening, and fibrous intimal thickening (Table 5). However, any vascular lesions did not show a direct relationship with the occurrence of end-stage renal disease (Fig. 2a, Log-rank test: p = 0.2). Even when analyzed separately for arterial wall thickening and fibrous intimal thinkening, no significant relationship was found (Fig. 2b and 2c, log-rank test: p = 0.06 and p = 0.6, respectively).

Table 4

Univariate hazards model of survival according to clinicopathological characteristics
Univariate hazard model
	HR (95% CI)	p-value
Vascular changes
Any vascular lesions	3.89 (0.49–31.09)	0.2
Arteriolar wall thickening	5.76 (0.72–46.2)	0.1
Fibrous intimal thickening	1.37 (0.37–5.15)	0.6
Pathological Features
Global glomerulosclerosis	1.05 (1.03–1.07)	0.00006*
Clinical Information
Age	1.05 (0.99–1.1)	0.067
eGFR	0.93 (0.9–0.97)	0.0004*
UPCR	1.15 (0.96–1.37)	0.13
BUN	1.14 (1.08–1.21)	0.000003*
Serum creatinine	3.264 (2.12–5.03)	0.00000009*
Albumin	0.37 (0.17–0.81)	0.013*

HR, hazard ratio; CI, confidence interval; eGFR, estimated glomerular filtration rate; UPCR, urine protein-to-creatinine ratio; BUN, blood urea nitrogen.

Table 5

Multivariate hazards model of survival according to clinicopathological characteristics
Multivariate hazard model
HR (95% CI)	p-value	HR (95% CI)	p-value	HR (95% CI)	p-value
Any vascular lesions		Arteriolar wall thickening		Fibrous intimal thickening
0.56 (0.03–9.57)	0.7	0.71 (0.05–10.17)	0.8	0.87 (0.036–21.04)	0.9
Global glomerulosclerosis
1.06 (1.02–1.1)	0.0018*	1.06 (1.02–1.100)	0.0025*	1.07 (1.01–1.13)	0.02*
eGFR
0.97 (0.93–1.01)	0.1	0.97 (0.93–1.01)	0.1	0.95 (0.89–1.02)	0.18
BUN
1.02 (0.9–1.15)	0.75	1.02 (0.91–1.16)	0.7	1.02 (0.88–1.18)	0.8
Serum creatinine
4.39 (1.43–13.47)	0.01*	4.38 (1.41–13.62)	0.01*	6.31 (1.43–27.78)	0.015*

HR, hazard ratio; CI, confidence interval; eGFR, estimated glomerular filtration rate; UPCR, urine protein-to-creatinine ratio; BUN, blood urea nitrogen.

Vascular lesions are frequently observed in renal biopsy specimens from patients with IgAN. However, the prognostic significance of these lesions remains unclear. Our study indicates that arterial wall thickening and fibrous intimal thickening are associated with a reduced eGFR and increased UPCR. These lesions also correlated with the presence of global sclerosis and tubular atrophy, consistent with the findings of other studies [6–9]. Notably, global sclerosis and high serum creatinine levels were observed and eventually lead to patients requiring dialysis, thereby suggesting the potential involvement of vasculopathies in the progression or prognosis of IgAN. Although our study was cross-sectional, the presence of these lesions implies the need for an aggressive treatment approach in affected patients.

The results indicate that arterial wall thickening and fibrous intimal thickening are related to hypertension, and decreased eGFR aligns with the findings of other studies [10–13]. While this association was also observed in the original Oxford cohort, it did not exhibit a significant relationship with kidney failure events, and as a result, vascular lesions were not included in the classification criteria. In our study, vascular lesions did not show a significant relationship with the occurrence of end-stage renal disease (Fig. 2a, log-rank test: p = 0.2). Even when analyzed separately for arterial wall thickening and fibrous intimal thickening, no significant relationship was found (Fig. 2b and 2c, log-rank test: p = 0.06 and p = 0.6, respectively). However, a case-control study by Huang et al. reported a significant relationship between the presence of vascular lesions and the transition to end-stage renal disease or death in patients with IgAN [13]. The discrepancy in the results may be attributed to the relatively small number of cases in our study, which resulted in a limited number of endpoint events. Nonetheless, in our study, arterial wall thickening showed a marginally significant correlation with the endpoint (p-value = 0.06), and we hypothesized that similar results could be obtained with an increased sample size and comprehensive eGFR follow-up data.

The current treatment approach for IgAN aims to decelerate renal damage progression, encompassing blood pressure and proteinuria control, through the use of RAAS blockade. In cases where serum creatinine levels are elevated and biopsy reveals features, such as endocapillary hypercellularity or crescents, or if there is proteinuria in the nephrotic range, immunosuppressors, such as steroids, may be employed [14]. In our study, individuals with vascular lesions had a high prevalence of hypertension. Arterial wall thickening and fibrous intimal thickening, both of which are associated with hypertension, are common vascular lesions. However, among individuals with vascular lesions, 45.5% were diagnosed with hypertension, leaving a substantial proportion without hypertension. This suggests that although high blood pressure may contribute to vascular lesions, it is also plausible that vascular lesions could lead to secondary hypertension. Further research on the impact of nonhypertensive intrarenal vascular lesions on the disease course could contribute to a more comprehensive understanding. If a robust correlation is established, interventions aimed at slowing the progression of IgAN, based on biopsy findings before the onset of proteinuria or hypertension, may become a viable treatment strategy.

Intrarenal vascular lesions in IgAN are linked to reduced eGFR and global glomerulosclerosis. Moreover, reduced eGFR and global glomerulosclerosis are correlated with the progression to end-stage renal disease. Although the direct correlation between vascular lesions and end-stage renal disease is not entirely clear, a marginally significant association (log-rank test, p = 0.06) was observed with arterial wall thickening. This study suggests the potential importance of vascular lesions in the prognosis of IgAN, encouraging further investigation using large cohort studies to establish a clarified association.

Availability of data and materials

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Competing interests

The authors have no conflict of interests to declare.

Ethics approval and consent to participate

The study protocol was approved by Institutional Review Board (IRB) of Kyungpook National University Hospital, Daegu, Korea (IRB FILE No. KNUH 2023-12-017, 8 January 2024) and has been conducted in full accordance with the Declaration of Helsinki. The study was retrospective therefore the Institutional Review Board (IRB) of Kyungpook National University Hospital, Daegu, Korea (IRB FILE No. KNUH 2023-12-017, 8 January 2024) waived the need for written informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Funding

None

Authors' contributions

Conception and design of study: Man-Hoon Han, Yong-Jin Kim

Acquisition of data: Jeong-Hoon Lim, Sun-Hee Park

Analysis and/or interpretation of data: Yuna Kang, DongJa Kim

Drafting the manuscript: Hyeon Tae Yang, Mee-seon Kim

Revising the manuscript critically for important intellectual content: Man-Hoon Han, Tae In Park , Hyeon Tae Yang

Acknowledgements

None

J.C. Rodrigues, M. Haas, H.N. Reich, IgA Nephropathy, Clin. J. Am. Soc. Nephrol. 12 (2017) 677–686. https://doi.org/10.2215/cjn.07420716.
H. Trimarchi, J. Barratt, D.C. Cattran, H.T. Cook, R. Coppo, M. Haas, Z.H. Liu, I.S. Roberts, Y. Yuzawa, H. Zhang, J. Feehally, Oxford classification of IgA nephropathy 2016: an update from the IgA nephropathy classification working group. Kidney Int. 91 (2017) 1014–1021. https://doi.org/10.1016/j.kint.2017.02.003.
M Haas, Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases, Am. J. Kidney Dis. 29 (1997) 829–842. https://doi.org/10.1016/s0272-6386(97)90456-x.
J. Wu, X. Chen, Y. Xie, N. Yamanaka, S. Shi, D. Wu, S. Liu, G. Cai, Characteristics and risk factors of intrarenal arterial lesions in patients with IgA nephropathy. Nephrol. Dial. Transplant. 20 (2005) 719–727. https://doi.org/10.1093/ndt/gfh716.
K. Matsushita, B.K. Mahmoodi, M. Woodward, J.R. Emberson, T.H. Jafar, S.H. Jee, K.R. Polkinghorne, A. Shankar, D.H. Smith, M. Tonelli, D.G. Warnock, C.P. Wen, J. Coresh, R.T Gansevoort, B.R. Hemmelgarn, A.S. Levey, Chronic Kidney Disease Prognosis C: Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate. JAMA. 307 (2012) 1941–1951. https://doi.org/10.1001/jama.2012.3954.
Y. Zhang, L. Sun, S. Zhou, Q. Xu, Q. Xu, D. Liu, L. Liu, R. Hu, S. Quan, G. Xing, Intrarenal arterial lesions are associated with higher blood pressure, reduced renal function and poorer renal outcomes in patients with IgA nephropathy. Kidney Blood Press. Res. 43 (2018) 639–650. https://doi.org/10.1159/000489290.
F.F. Chen, X.J. Yu, H. Wang, X. Zhang, Y. Tan, Z. Qu, S.X. Wang, F. Yu, M. Chen, M.H. Zhao, Clinical value of the renal pathologic scoring system in complement-mediated thrombotic microangiopathy. Ren. Fail. 45 (2023) 2161396. https://doi.org/10.1080/0886022x.2022.2161396.
Q. Cai, S. Shi, S. Wang, Y. Ren, W. Hou, L. Liu, J. Lv, M. Haas, H. Zhang, Microangiopathic lesions in IgA nephropathy: A cohort study. Am. J. Kidney Dis. 74 (2019) 629–639. https://doi.org/10.1053/j.ajkd.2019.03.416.
C.H. Zeng, W. Le, Z. Ni, M. Zhang, L. Miao, P. Luo, R. Wang, Z. Lv, J. Chen, J. Tian, N. Chen, X. Pan, P. Fu, Z. Hu, L. Wang, Q. Fan, H. Zheng, D. Zhang, Y. Wang, Y. Huo, H. Lin, S. Chen, S. Sun, Y. Wang, Z. Liu, D. Liu, L. Ma, T. Pan, A. Zhang, X. Jiang, C. Xing, B. Sun, Q. Zhou, W. Tang, F. Liu, Y. Liu, S. Liang, F. Xu, Q. Huang, H. Shen, J. Wang, Y. Shyr, S. Phillips, S. Troyanov, A. Fogo, Z-.H. Liu, A multicenter application and evaluation of the Oxford classification of IgA nephropathy in adult Chinese patients. Am. J. Kidney Dis. 60 (2012) 812–820. https://doi.org/10.1053/j.ajkd.2012.06.011.
R. Coppo, S. Troyanov, S. Bellur, D. Cattran, H.T. Cook, J. Feehally, I.S.D Roberts, L. Morando, R. Camilla, V. Tesar, S. Lunberg, L.Gesualdo, F. Emma, C. Rollino, A. Amore, M. Praga, S. Feriozzi, G. Segoloni, A. Pani, G. Cancarini, M. Durlik, E. Moggia, G. Mazzucco, C. Giannakakis, E. Honsova, B.B. Sundelin, A.M. Di Palma, F. Ferrario, E. Gutierrez, A.M. Asunis, J. Barratt, R. Tardanico, A. Perkowska-Ptasinska VALIGA study of the ERA-EDTA Immunonephrology Working Group, Validation of the Oxford classification of IgA nephropathy in cohorts with different presentations and treatments. Kidney Int. 86 (2014) 828–836. https://doi.org/10.1038/ki.2014.63.
A.M. Herzenberg, A.B. Fogo, H.N. Reich, S. Troyanov, N. Bavbek, A.E. Massat, T.E. Hunley, M.A. Hladunewich, B.A. Julian, F.C. Fervenza, D.C. Cattran, Validation of the Oxford classification of IgA nephropathy. Kidney Int. 80 (2011) 310–317. https://doi.org/10.1038/ki.2011.126.
S.F. Shi, S.X. Wang, L. Jiang, Ji-.C. Lv, Li-.J. Liu, Yu-.Q. Chen, S-.N. Zhu, G. Liu, W-.Z. Zou, H. Zhang, H-.Y. Wang, Pathologic predictors of renal outcome and therapeutic efficacy in IgA nephropathy: Validation of the Oxford classification. Clin. J. Am. Soc. Nephrol. 6 (2011) 2175–2184. https://doi.org/10.2215/cjn.11521210.
Z. Huang, Y. Hu, B. Chen, Y. Liang, D. Li, W. Qiu, J. Zhang, C. Chen, Clinical significance of intrarenal vascular lesions in non-hypertensive patients with IgA nephropathy. J. Nephrol. 36 (2023) 429–440. https://doi.org/10.1007/s40620-022-01511-w.
Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group, KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 100 (2021) S1–S276. https://doi.org/10.1016/j.kint.2021.05.021.

No competing interests reported.

Download PDF

Journal Publication

published 16 Oct, 2024

Read the published version in BMC Nephrology →

Editorial decision: Revision requested
23 Aug, 2024
Reviews received at journal
21 Aug, 2024
Reviews received at journal
21 Aug, 2024
Reviewers agreed at journal
14 Aug, 2024
Reviews received at journal
14 Aug, 2024
Reviewers agreed at journal
13 Aug, 2024
Reviewers agreed at journal
11 Aug, 2024
Reviewers agreed at journal
11 Aug, 2024
Reviewers invited by journal
11 Aug, 2024
Editor invited by journal
08 Aug, 2024
Editor assigned by journal
08 Aug, 2024
Submission checks completed at journal
08 Aug, 2024
First submitted to journal
31 Jul, 2024

You are reading this latest preprint version

Significance of intrarenal vascular lesions in Ig A nephropathy prognosis

Status:

Journal Publication

Version 1

Abstract

Background

Methods

Results

Conclusion

Figures

Background

Methods

Patients

Histological evaluation

Outcome

Statistical analysis

Results

Clinical and pathologic features related to arteriolar wall thickening

Clinical and pathological features related to fibrous intimal thickening

Clinical and pathological features according to any vascular lesions

Discussion

Conclusion

Declarations

References

Additional Declarations

Status:

Journal Publication

Version 1