Limitations of RAS Blockade in IgA Nephropathy

Chapter

Recommendation statement

Grade

10.2

Antiproteinuric and antihypertensive therapy

10.2.1

We recommend long-term ACEI or ARB treatment when proteinuria is >1 g/day, with up-titration of the drug depending on blood pressure

10.2.2

We suggest ACEI or ARB treatment if proteinuria is between 0.5 and 1 g/day (in children, between 0.5 and 1 g/day per 1.73 m²)

10.3.3

We suggest the ACEI or ARB be titrated upward as far as tolerated to achieve proteinuria <1 g/day

10.3.4

In IgAN, use blood pressure treatment goals of <130/80 mmHg in patients with proteinuria <1 g/day and <125/75 mmHg when initial proteinuria is >1 g/day

Not graded

10.3

Corticosteroids

10.3.1

We suggest that patients with persistent proteinuria ≥1 g/day, despite 3–6 months of optimized supportive care (including ACEI or ARBs and blood pressure control) and GFR >50 mL/min per 1.73 m², receive a 6-month course of corticosteroid therapy

(1) Strength of recommendation: grade 1–2

Grade 1, “we recommend”

– Implications for clinicians: Most patients should receive the recommended course of action

– Implications for patients: Most people in your situation would want the recommended course of action and only a small proportion would not

– Implications for policy: The recommendation can be evaluated as a candidate for developing a policy or a performance measure

Grade 2, “we suggest”

– Implications for clinicians: The majority of people in your situation would want the recommended course of action, but many would not

– Implications for patients: Different choices will be appropriate for different patients. Each patient needs help to arrive at a management decision consistent with her or his values and preferences

– Implications for policy: The recommendation is likely to require substantial debate and involvement of stakeholders before policy can be determined

(2) Quality of evidence: grade A–D

Grade A, “high”

– We are confident that the true effect lies close to that of the estimate of the effect

Grade B, “moderate”

– The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different

Grade C, “low”

– The true effect may be substantially different from the estimate of the effect

Grade D, “very low”

– The estimate of effect is very uncertain and often will be far from the truth

ACEI angiotensin-converting enzyme inhibitor, ARB angiotensin receptor blocker, GFR glomerular filtration rate, IgAN IgA nephropathy, KDIGO kidney disease: improving global outcomes, RAS renin-angiotensin system

Table 16.2

RAS blockade and use of corticosteroids in IgAN patients in Japanese Evidence-Based Clinical Practice Guideline for CKD 2013 [6, 56] and IgAN 2014

No	Clinical questions and statements	Grade
2	Are RAS inhibitors recommended for decreasing urinary protein and preserving renal function in patients with IgAN?
	We recommend treatment with RAS inhibitors for patients with proteinuria ≥1 g/day and eGFR ≥30 mL/min/1.73 m² (CKD G1 to G3b) because of their effect of preservation of renal function	A
	We suggest treatment with RAS inhibitors if proteinuria is between 0.5 and 1.0 g/day because of their antiproteinuric effect	C1
3	Are corticosteroids recommended for decreasing urinary protein and preserving renal function in patients with IgAN?
	We recommend that patients with proteinuria ≥1 g/day and eGFR ≥60 mL/min/1.73 m² (CKD G1 to G2) receive a 6-month course of high-dose oral corticosteroids therapy (6-month regime of oral prednisone starting with 0.8–1 mg/kg/day for 2 months and then reduced gradually for the next 4 months)	B
	We recommend that patients with proteinuria ≥1 g/day and eGFR ≥60 mL/min/1.73 m² (CKD G1 to G2) receive high-dose pulse corticosteroids therapy (i.v. bolus injections of 1 g methylprednisolone for 3 days each at months 1, 3, and 5, followed by 0.5 mg/kg oral prednisone on alternate days for 6 months)	B
	We tentatively suggest using corticosteroids for patients with proteinuria less than 1 g/day and eGFR ≥60 mL/min/1.73 m² (CKD G1 to G2) because of their antiproteinuric effect	C1

Strength of recommendation: grade A–D

Grade A, strongly recommended because the scientific basis is strong

Grade B, recommended because there is some scientific basis

Grade C1, recommended despite having only a weak scientific basis

Grade C2, not recommended because there is only a weak scientific basis

Grade D, not recommended because scientific evidence shows the treatment to be ineffective or harmful

ACEI angiotensin-converting enzyme inhibitor, ARB angiotensin receptor blocker, IgAN IgA nephropathy, RAS renin-angiotensin system

16.2 RAS Blockade in IgA Nephropathy Patients in KDIGO Guideline and Japanese Guidelines

In KDIGO Clinical Practice Guideline for Glomerulonephritis, strength of recommendation of RAS blockade is different between IgAN patients with proteinuria >1 g/day and those with proteinuria <1 g/day. KDIGO guideline recommends RAS blockade in IgAN patients with proteinuria >1 g/day (statement 10.2.1, grade 1B), whereas it suggests RAS blockade in those with proteinuria between 0.5 and 1 g/day (statement 10.2.2, grade 2D) (Table 16.1). The rationales for the different strength of recommendation on RAS blockade are, first, that moderate-quality evidence identified proteinuria >1 g/day as a risk factor of accelerated decline in GFR [8] and, second, that the majority of randomized trials using ACEI or ARB recruited IgAN patients mainly with proteinuria >1 g/day (Tables 16.3a, 16.3b, 16.3c, 16.3d, 16.4a, 16.4b, 16.4c, 16.4d, 16.5a, 16.5b, 16.5c, and 16.5d). Interestingly, KDIGO guideline suggests IgAN patients with persistent proteinuria ≥1 g/day, despite 3–6 months of optimized supportive care (including ACEIs or ARBs and blood pressure control), and GFR >50 mL/min per 1.73 m², receive a 6-month course of corticosteroid therapy (statement 10.3.1, grade 2C). As an initial therapy in IgAN patients with proteinuria ≥1 g/day, RAS blockade takes priority over corticosteroid therapy.

Table 16.3a

Study protocols of RCTs assessing efficacy of ACEI vs. no RAS blockade in IgAN patients

Author year	Interventions (dose)	Duration	Age	BP	Renal function	UP	Histology
Parallel group trials
Praga 2003 [9]	Enalapril (≤40 mg)	ND (76 months)	Adult	0–2 antihypertensive drugs	SCr ≤1.5 mg/dL	≥0.5 g/day	ND
Praga 2003 [9]	No RAS blockade	ND (76 months)	Adult	No malignant hypertension	SCr ≤1.5 mg/dL	≥0.5 g/day	ND
Li 2013 [10]	Ramipril (2.5 mg)	60 months	18–65 years	Normal blood pressure	SCr <120 μmol/L	<0.5 g/day	ND
Li 2013 [10]	No treatment	60 months	18–65 years	Normal blood pressure	SCr <120 μmol/L	<0.5 g/day	ND
Coppo 2007 [11]	Benazepril (≤0.2 mg/kg)	36 months	3–35 years	BP <140/90 mmHg (adults)	eGFR >50 mL/min/1.73 m²	1.0–3.4 g/day	ND
Coppo 2007 [11]	Placebo	36 months	3–35 years	BP <95 % (children)	eGFR >50 mL/min/1.73 m²	1.0–3.4 g/day	ND
Kanno 2005 [12]	ACEI (≤2 mg)^a	≥3 years	ND	No previous ACEI	ND	ND	ND
Kanno 2005 [12]	Amlodipine (5 mg)	≥3 years	ND	No previous ACEI	ND	ND	ND
Ruggenenti 2000 [13]	Ramipril (≤5 mg)	63 months	18–70 year	BP <220/115 mmHg	Ccr 20–70 mL/min/1.73 m²	≥1.0 g/day	ND
Ruggenenti 2000 [13]	Placebo^b	63 months	18–70 year	BP <220/115 mmHg	Ccr 20–70 mL/min/1.73 m²	≥1.0 g/day	ND
Bannister 1995 [14]	Enalapril (ND)	12 months	ND	Hypertension	GFR 30–90 mL/min	ND	ND
Bannister 1995 [14]	Nifedipine (ND)	12 months	ND	Hypertension	GFR 30–90 mL/min	ND	ND
Nakamura 2000 [15]	Trandolapril (2 mg)	3 months	ND	Normal blood pressure	Ccr >80 mL/min/1.73 m²	≤3.0 g/day	ND
	Candesartan (8 mg)			(BP <140/90 mmHg)
	Verapamil (120 mg)
	Placebo
Crossover trials
Maschio 1994 [16]	Fosinopril (20 mg)	4 months	ND	Normal blood pressure	SCr <1.4 mg/dL	≥1.0 g/day	ND
Maschio 1994 [16]	Placebo	4 months	ND	(BP <140/90 mmHg)	Ccr >90 mL/min/1.73 m²	≥1.0 g/day	ND
Ikeda 1989 [17] (sub)	Captopril (ND)	ND	ND	ND	ND	ND	ND
Ikeda 1989 [17] (sub)	Nicardipine (ND)	ND	ND	ND	ND	ND	ND

ACEI angiotensin-converting enzyme inhibitor, BP blood pressure, Ccr creatinine clearance, CKD chronic kidney disease, eGFR estimated GFR, GFR glomerular filtration rate, IgAN IgA nephropathy, RAS renin-angiotensin system, SCr serum creatinine, UP urinary protein

^aTemocapril (≤2 mg) or trandolapril (≤2 mg)

^bThe patients’ code was opened at 27th month of randomization

Table 16.3b

Baseline characteristics of IgAN patients included in RCTs assessing efficacy of ACEI vs. no RAS blockade

Author year	Interventions	N	Age	SBP/DBP or MAP	SCr		GFR	UP	Histology
Author year	Interventions	N	(Year)	(mmHg)	(mg/dL)		(mL/min)	UP	Histology
Parallel group trials
Praga 2003 [9]	Enalapril	23	27.8 ± 12	102 ± 11	1 ± 0.2	Ccr	102 ± 25	2 ± 1.3 g/day	ND
Praga 2003 [9]	No RAS blockade	21	29.9 ± 12.3	98 ± 12	0.9 ± 0.2		99 ± 22	1.7 ± 0.8
Li 2013 [10]	Ramipril	30	42.2 ± 11.0	115.5 ± 13.0/69.6 ± 10.3	0.88 ± 0.19^c	eGFR	106.8 ± 20.9 per1.73 m²	0.10 ± 0.13 g/gCr	Haas’ [57] and
Li 2013 [10]	No treatment	30	41.0 ± 7.5	114.2 ± 16.3/70.1 ± 9.3	0.85 ± 0.14^c		102.9 ± 15.2	0.12 ± 0.13 g/gCr	To’s [58]
Coppo 2007 [11]	Benazepril	32	21.8 ± 6.3	122.59 ± 9.0/77.81 ± 8.0	ND	Ccr	113.2 ± 23.5 per 1.73 m²	1.61 ± 0.70 g/day per 1.73 m²	ND
Coppo 2007 [11]	Placebo	34	19.3 ± 6.1	117.06 ± 11.0/72.09 ± 9.0			114.1 ± 19.0	1.87 ± 0.74
Kanno 2005 [12]	ACEI^a	26	35 ± 10^b	143 ± 15^b/87 ± 10^b	1.07 ± 0.66^b	Ccr	92.8 ± 31.6^b	1.09 ± 0.82^b g/day	TIF index
Kanno 2005 [12]	Amlodipine	23	35 ± 14^b	140 ± 14^b/83 ± 10^b	1.02 ± 0.38^b		90.8 ± 34.1^b	1.10 ± 0.72^b
Ruggenenti 2000 [13]	Ramipril	39	42.3 ± 12.9	142.8 ± 16.3/91.8 ± 9.9	1.96 ± 0.73	Cio	48.1 ± 20.3 per 1.73 m²	3.05 ± 2.17 g/day	ND
Ruggenenti 2000 [13]	Placebo	36	45.9 ± 11.2	137.6 ± 12.8/89.3 ± 8.0	2.12 ± 0.94		44.2 ± 16.7	3.19 ± 1.93
Bannister 1995 [14]	Enalapril	13	49 [34–74]	116 ± 9.0^b	ND	C_DTPA	74.6 ± 24.9^b	ND	ND
Bannister 1995 [14]	Nifedipine	10	53 [32–69]	114 ± 7.5^b			62.5 ± 13.8^b
Nakamura [15] 2000	Trandolapril	8	32.6 [18–54]	118 ± 14/80 ± 6	0.8 ± 0.2	Ccr	108 ± 16 per 1.73 m²	1.9 ± 0.7 g/day	ND
	Candesartan	8		118 ± 16/78 ± 6	0.7 ± 0.2		112 ± 14	1.8 ± 0.8
	Verapamil	8		116 ± 12/82 ± 8	0.9 ± 0.2		110 ± 12	1.8 ± 0.6
	Placebo	8		120 ± 12/80 ± 8	0.8 ± 0.2		112 ± 12	1.6 ± 0.6
Crossover trials
Maschio [16] 1994	Fosinopril	39	33.2 ± 11.4 [18–58]	92.8 ± 9.1	1.0 ± 0.2	Ccr	103 ± 23 per 1.73 m²	1.74 ± 0.84 g/day	ND
Maschio [16] 1994	Placebo	39	33.2 ± 11.4 [18–58]	92.8 ± 9.1	1.0 ± 0.2	Ccr	103 ± 23 per 1.73 m²	1.74 ± 0.84 g/day	ND
Ikeda [17] 1989(sub)	Captopril	4	40.5 ± 12.6	167.5 ± 21.4/110.0 ± 14.0	ND	Ccr	78.0 ± 20.5	2.9 ± 0.6 g/day	ND
Ikeda [17] 1989(sub)	Nicardipine	4	40.5 ± 12.6	167.5 ± 21.4/110.0 ± 14.0	ND	Ccr	78.0 ± 20.5	2.9 ± 0.6 g/day	ND

Mean ± SD, median [range]

ACEI angiotensin-converting enzyme inhibitor, Ccr creatinine clearance, C _DTPA^99mTc-diethylenetriaminepentaacetic acid clearance, Cio iohexol clearance, Cr creatinine, eGFR estimated GFR, GFR glomerular filtration rate, IgAN IgA nephropathy, MAP mean arterial pressure, RAS renin-angiotensin system, RCT randomized controlled trial, SBP/DBP systolic and diastolic blood pressure, SCr serum creatinine, TIF tubulointerstitial fibrosis, UP urinary protein

^aTemocapril or trandolapril

^bSE was multiplied by √N to calculate SD

^cAn original unit, μmol/L, was divided by 88.4 for conversion to mg/dL

Table 16.3c

Outcomes of renal function in RCTs assessing efficacy of ACEI vs. no RAS blockade in IgAN patients

Author year	Interventions	N	Follow-up	ESKD	ΔSCr ≥100 %	ΔSCr ≥50 %	SCr at last visit		GFR at last visit	ΔGFR
Author year	Interventions	N	Follow-up	(N)	(N)	(N)	(mg/dL)		(mL/min)	(mL/min per 1.73 m²)
Parallel group trials
Praga 2003 [9]	Enalapril	23	78 ± 37 [36–120] months	ND	ND	3	1.2 ± 0.5	Ccr	95 ± 30	ND
Praga 2003 [9]	No RAS blockade	21	74 ± 36 [29–108]	ND	ND	12*	1.9 ± 1.9	Ccr	64 ± 31*	ND
Li 2013 [10]	Ramipril	30	60 month	ND	ND	ND	ND	eGFR	108.1 ± 29.0 per 1.73 m²	0.39 ± 2.57 per year
Li 2013 [10]	No treatment	30	60 month	ND	ND	ND	ND	eGFR	105.7 ± 17.7	0.59 ± 1.63
Coppo 2007 [11]	Benazepril	32	35^b [0–58] mo	0	ND	ND	ND	Ccr	124.0 ± 31 per 1.73 m²	ND
Coppo 2007 [11]	Placebo	34	38^b [3–53] mo	0	ND	ND	ND	Ccr	109.3 ± 29.8*	ND
Kanno 2005 [12]	ACEI^a	26	≥36 months	ND	ND	ND	1.18 ± 1.33^d	Ccr	85.5 ± 28.0^d	ND
Kanno 2005 [12]	Amlodipine	23	≥36 months	ND	ND	ND	1.23 ± 2.01^d	Ccr	85.5 ± 35.5^d	ND
Ruggenenti 2000 [13]	Ramipril	39	30.0^b (16.4–47.5) mo^c	7	ND	ND	ND	Cio	ND	0.36 ± 0.56^d per month
Ruggenenti 2000 [13]	Placebo^b	36	30.0^b (16.4–47.5) mo^c	9	ND	ND	ND	Cio	ND	0.55 ± 0.78^d
Bannister 1995 [14]	Enalapril	13	12 months	ND	ND	ND	ND		ND	ND
Bannister 1995 [14]	Nifedipine	10	12 months	ND	ND	ND	ND		ND	ND
Nakamura 2000 [15]	Trandolapril	8	3 months	ND	ND	ND	0.8 ± 0.3	Ccr	110 ± 14 per 1.73 m²	ND
	Candesartan	8					0.8 ± 0.2		110 ± 16
	Verapamil	8					0.8 ± 0.2		106 ± 14
	Placebo	8					0.8 ± 0.3		110 ± 12
Crossover trials
Maschio 1994 [16]	Fosinopril	39	3 months	ND	ND	ND	ND	Ccr	105 ± 23 per 1.73 m²	ND
Maschio 1994 [16]	Placebo	39	3 months	ND	ND	ND	ND	Ccr	107 ± 25	ND
Ikeda 1989 [17] (sub)	Captopril	4	ND	ND	ND	ND	ND	Ccr	71.9 ± 25.3	ND
Ikeda 1989 [17] (sub)	Nicardipine	4	ND	ND	ND	ND	ND	Ccr	77.5 ± 20.4	ND

Mean ± SD, [range], (25–75 %)

ACEI angiotensin-converting enzyme inhibitor, Ccr creatinine clearance, C _DTPA^99mTc-diethylenetriaminepentaacetic acid clearance, Cio iohexol clearance, Cr creatinine, eGFR estimated GFR, ESKD end-stage kidney disease, GFR glomerular filtration rate, IgAN IgA nephropathy, RAS renin-angiotensin system, RCT randomized controlled trial, TIF tubulointerstitial fibrosis, ΔGFR a decrease in GFR from the baseline value, ΔSCr an increase in serum creatinine from the baseline value

*P < 0.05 (vs. ACEI intervention)

^aTemocapril or trandolapril

^bMedian

^cFollow-up period of the whole cohort including IgAN patients (N = 75) and other CKD patients (N = 277)

^dSE was multiplied by √N to calculate SD

Table 16.3d

Outcomes of urinary protein in RCTs assessing efficacy of ACEI vs. no RAS blockade in IgAN patients

Author year	Interventions	N	Follow-up	At last visit		At 12th month		At 3rd month		Histology
Author year	Interventions	N	Follow-up	UP (g/day)	ΔUP (%)	UP (g/day)	ΔUP (%)	UP (g/day)	ΔUP (%)	Histology
Parallel group trials
Praga 2003 [9]	Enalapril	23	78 ± 37 [36–120] months	0.9 ± 1	ND	1.2 ± 1.1	36 ± 40.1	ND	ND	ND
Praga 2003 [9]	No RAS blockade	21	74 ± 36 [29–108]	2 ± 1.8*	ND	1.8 ± 1.5	−23 ± 79*	ND	ND	ND
Li 2013 [10]	Ramipril	30	60 months	ND	ND	ND	ND	ND	ND	ND
Li 2013 [10]	No treatment	30	60 months	ND	ND	ND	ND	ND	ND	ND
Coppo 2007 [11]	Benazepril	32	35^b [0–58] mo	0.94 ± 0.98 per 1.73m²	ND	0.96 ± 0.68 per 1.73 m²	ND	ND	ND	ND
Coppo 2007 [11]	Placebo	34	38^b [3–53] mo	1.80 ± 1.34*	ND	ND	ND	ND	ND	ND
Kanno 2005 [12]	ACEI^a	26	≥36 months	0.79 ± 1.84^d	ND	ND	ND	ND	ND	ND
Kanno 2005 [12]	Amlodipine	23	≥36 months	1.33 ± 2.91^d	ND	ND	ND	ND	ND	ND
Ruggenenti 2000 [13]	Ramipril	39	30.0^b (16.4–47.5) mo^c	ND	ND	ND	ND	ND	ND	ND
Ruggenenti 2000 [13]	Placebo^b	36	30.0^b (16.4–47.5) mo^c	ND	ND	ND	ND	ND	ND	ND
Bannister 1995 [14]	Enalapril	13	12 months	ND	ND	ND	ND	ND	ND	ND
Bannister 1995 [14]	Nifedipine	10	12 months	ND	ND	ND	ND	ND	ND	ND
Nakamura 2000 [15]	Trandolapril	8	3 months	1.2 ± 0.5	36.8 ± 15.2	ND	ND	1.2 ± 0.5	36.8 ± 15.2	ND
	Candesartan	8		1.1 ± 0.6	38.9 ± 16.6			1.1 ± 0.6	38.9 ± 16.6
	Verapamil	8		1.4 ± 0.5	22.2 ± 8.4*			1.4 ± 0.5	22.2 ± 8.4*
	Placebo	8		1.7 ± 0.7	ND			1.7 ± 0.7	ND
Crossover trials
Maschio 1994 [16]	Fosinopril	39	3 months	1.37 ± 0.98	ND	ND	ND	1.37 ± 0.98	ND	ND
Maschio 1994 [16]	Placebo	39	3 months	1.79 ± 1.20*	ND	ND	ND	1.79 ± 1.20	ND	ND
Ikeda 1989 [17]	Captopril	4	ND	1.4 ± 0.6	ND	ND	ND	ND	ND	ND
Ikeda 1989 [17]	Nicardipine	4	ND	2.5 ± 0.7	ND	ND	ND	ND	ND	ND

Mean ± SD, [range], (25–75 %)

ACEI angiotensin-converting enzyme inhibitor, IgAN IgA nephropathy, RAS renin-angiotensin system, RCT randomized controlled trial, UP urinary protein, ΔUP decrease in UP from the baseline value

*P < 0.05 (vs. ACEI intervention)

^aTemocapril or trandolapril

^bMedian

^cFollow-up period of the whole cohort including IgAN patients (N = 75) and other CKD patients (N = 277)

^dSD was calculated multiplying SE by √N

Table 16.4a

Study protocols of RCTs assessing efficacy of ARB vs. no RAS blockade in IgAN patients

Author year	Interventions (dose)	Duration	Age(yr)	BP	Renal function	UP (g/day)	Histology
Parallel group trials
Li 2006 [18]	Valsartan (≤160 mg)	104 weeks	≥18	No malignant hypertension	SCr <2.8 mg/dL and UP ≥1.0 g/d	ND
Li 2006 [18]	Placebo	104 weeks	≥18	No malignant hypertension	or SCr 1.4–2.8 mg/dL	ND
Horita 2007 [19]	Losartan (12.5 mg) + PSL (≤30 mg)	24 months	ND	Normal blood pressure	eCcr >50 mL/min/1.73 m²	1.0–2.6	Katafuchi’s scale [54] 4–7
Horita 2007 [19]	PSL (≤30 mg)	24 months	ND	(BP <140/90 mmHg)	eCcr >50 mL/min/1.73 m²	1.0–2.6	Katafuchi’s scale [54] 4–7
Shimizu 2008 [20]	Losartan (≤25 mg)	12 months	ND	Normal blood pressure	eGFR >50 mL/min/1.73 m²	≥0.4	ND
Shimizu 2008 [20]	Antiplatelet	12 months	ND	(BP <140/90 mmHg)	eGFR >50 mL/min/1.73 m²	≥0.4	ND
Xie 2011 [21]	Losartan (100 mg) + MZR (≤250 mg)	12 months	14–70	ND	SCr <4.0 mg/dL^a	0.5–3.5	ND
	Losartan (100 mg)
	MZR (≤250 mg)
Nakamura 2000 [15]	Trandolapril (2 mg)	3 months	ND	Normal blood pressure	Ccr >80 mL/min/1.73 m²	≤3.0	ND
	Candesartan (8 mg)			(BP <140/90 mmHg)
	Verapamil (120 mg)
	Placebo
Park 2003 [22]	Losartan (50 mg)	12 weeks	ND	Hypertension	SCr <3.0 mg/dL	≥1.0	ND
Park 2003 [22]	Amlodipine (5 mg)	12 weeks	ND	Systolic BP ≤210 mmHg	SCr <3.0 mg/dL	≥1.0	ND

BP blood pressure, Ccr creatinine clearance, CKD chronic kidney disease, eCcr estimated Ccr, eGFR estimated glomerular filtration rate, MZR mizoribine, PSL prednisolone, SCr serum creatinine, UP urinary protein

^aAn original unit, μmol/L, was divided by 88.4 for conversion to mg/dL

Table 16.4b

Baseline characteristics of IgAN patients included in RCTs assessing efficacy of ARB vs. no RAS blockade

Author year	Interventions	N	Age	SBP/DBP or MAP	SCr		GFR	UP	Histology
Author year	Interventions	N	(Year)	(mmHg)	(mg/dL)		(mL/min)	(g/day)	Histology
Parallel group trial
Li 2006 [18]	Valsartan	54	40 ± 10	136 ± 20/81 ± 11	1.11 ± 0.48	eGFR	87 ± 36 per 1.73m²	1.8 ± 1.2	ND
Li 2006 [18]	Placebo	55	41 ± 9	137 ± 17/83 ± 14	1.29 ± 0.54	eGFR	78 ± 38	2.3 ± 1.7	ND
Horita 2007 [19]	Losartan + PSL	20	34 ± 12	120 ± 8/73 ± 6	0.8 ± 0.2	Ccr	104 ± 36 per 1.73 m²	1.6 ± 0.6	Katafuchi’s [59]
Horita 2007 [19]	PSL	18	32 ± 10	121 ± 7/75 ± 7	0.7 ± 0.1	Ccr	103 ± 28	1.6 ± 0.4	Katafuchi’s [59]
Shimizu 2008 [20]	Losartan	18	36.0 ± 8.5	119.3 ± 10.8/74.8 ± 7.5	1.0 ± 0.2	eGFR	72.0 ± 15.9	0.81 ± 0.52	Taneda’s [60]
Shimizu 2008 [20]	Antiplatelet	18	35.7 ± 8.1	122.1 ± 9.6/73.4 ± 12.1	0.9 ± 0.2	eGFR	75.4 ± 18.1	0.73 ± 0.36	Taneda’s [60]
Xie 2011 [21]	Losartan + MZR	34	33.68 ± 10.29	101.15 ± 9.94	0.96 ± 0.37^a	eGFR	91.50 ± 29.83 per 1.73 m²	1.21 ± 0.56	ND
	MZR	35	33.63 ± 11.71	97.61 ± 8.54	0.90 ± 0.25^a		95.63 ± 28.31	1.35 ± 0.74
	Losartan	30	33.67 ± 11.62	101.13 ± 9.88	0.88 ± 0.26^a		97.85 ± 32.87	1.12 ± 0.54
Nakamura 2000 [15]	Trandolapril	8	32.6 [18–54]	118 ± 14/80 ± 6	0.8 ± 0.2	Ccr	108 ± 16 per 1.73 m²	1.9 ± 0.7	ND
	Candesartan	8		118 ± 16/78 ± 6	0.7 ± 0.2		112 ± 14	1.8 ± 0.8
	Verapamil	8		116 ± 12/82 ± 8	0.9 ± 0.2		110 ± 12	1.8 ± 0.6
	Placebo	8		120 ± 12/80 ± 8	0.8 ± 0.2		112 ± 12	1.6 ± 0.6
Park 2003 [22]	Losartan	20	39.3 ± 8.7	131 ± 16/89 ± 9	ND	Ccr	63 ± 22 per 1.73 m²	2.3 ± 1.5	ND
Park 2003 [22]	Amlodipine	16	44.3 ± 13.4	131 ± 12/86 ± 11	ND	Ccr	63 ± 24	2.1 ± 0.7	ND

Mean ± SD, [range]

ARB angiotensin II receptor blocker, Ccr creatinine clearance, DBP diastolic blood pressure, eGFR estimated GFR, GFR glomerular filtration rate, IgAN IgA nephropathy, MAP mean arterial pressure, MZR mizoribine, PSL prednisolone, RAS renin-angiotensin system, RCT randomized controlled trial, SBP systolic blood pressure, SCr serum creatinine, UP urinary protein

^aAn original unit, μmol/L, was divided by 88.4 for conversion to mg/dL

Table 16.4c

Outcomes of renal function in RCTs assessing efficacy of ARB vs. no RAS blockade in IgAN patients

Author year	Interventions	N	Follow-up	ESKD	ΔSCr ≥100 %	ΔSCr ≥50 %	SCr at last visit		GFR at last visit	ΔGFR
Author year	Interventions	N	Follow-up	(N)	(N)	(N)	(mg/dL)		(mL/min)	(mL/min)
Parallel group trial
Li 2006 [18]	Valsartan	54	104 weeks	ND	1	ND	ND	eGFR	72.36 ± 34.20 per 1.73 m²	5.62 ± 6.79 per year
Li 2006 [18]	Placebo	55	104 weeks	ND	4	ND	ND	eGFR	63.39 ± 34.79	6.98 ± 6.17
Horita 2007 [19]	Losartan + PSL	20	24 months	ND	ND	0	0.8 ± 0.2	Ccr	100 ± 38 per 1.73 m²	ND
Horita 2007 [19]	PSL	18	24 months	ND	ND	4*	0.9 ± 0.2	Ccr	84 ± 34	ND
Shimizu 2008 [20]	Losartan	18	12 months	ND	ND	ND	0.9 ± 0.3	eGFR < div class='tao-gold-member'> Only gold members can continue reading. Log In or Register to continue Share this: Click to share on Twitter (Opens in new window) Click to share on Facebook (Opens in new window) Related posts: Differences in Etiology and Treatment in Scandinavian Countries How Different Are the Current Understandings of Treatments for IgA Nephropathy? Beyond the Differences in Tonsillectomy in IgA Nephropathy: From Rationale To Indications in Patients IgA Nephropathy from the VALIGA European Study: Differences in Treatment Approaches Within Europe Is IgA Nephropathy a Single Disease? Complement Activation Stay updated, free articles. Join our Telegram channel Tags: Pathogenesis and Treatment in IgA Nephropathy Jul 4, 2016 \| Posted by admin in NEPHROLOGY \| Comments Off on Limitations of RAS Blockade in IgA Nephropathy Full access? Get Clinical Tree Get Clinical Tree app for offline access Get Clinical Tree app for offline access