Late Onset Azotemia from RAAS Blockade in CKD Patients with Normal Renal Arteries and No Precipitating Risk Factors

Figures & data

Figure 1. Spectrum of associated precipitating risk factors in 100 CKD patients at enrollment. Abbreviations: RAS = renal artery stenosis, LORFFAB = Late onset renal failure from angiotensin blockade.

Table 1 Profile of antihypertensive treatment in 5 patients with LORFFAB

Patient number	Angiotensin blocking agent/dose	Months on stable dose of ABA	Number of antihypertensive agents	Substitute antihypertensive agent	Initial MABP	Last clinic MABP
1	Lisinopril 20 mg, daily	21	5	Amlodipine 5 mg, BID	104	91
2	Candesartan 16 mg, daily	60	3	Dose reduced to 8 mg, daily	92	111
3	Lisinopril 40 mg, daily	47	4	None	94	89
4	Lisinopril 5 mg, daily	28	2	Hydralazine 10 mg, twice daily	93	113
5	Lisinopril 20 mg, daily	17	3	Hydralazine 10 mg, twice daily	90	103

Figure 2. Changes in eGFR in a 44-year-old hypertensive Caucasian woman with stable SLE who presented in November 2002 to start dialysis after discontinuation of lisinopril.

Table 2 A critical appraisal of the large randomized RAAS blockade trials.[1–5]

TRIAL	Year Published	Study Size, n	RAAS Blocking Drugs	Indication for RAAS Blockade	Mean Drug Dosemg/d	Maxim Recom Drug Dose(mg/d)	Mean Age (years)	Follow up (mths)	Study ExclusionS creat (mg/dl)	Baseline Mean S creat (mg/dl)	Baseline Mean Cr Cleara(ml/min)	% DM	Doublingof S creat Rx vs Placebo (%)/Miscellanous	Inc Scr/ARFRx vs Pleceb (%)	K>5.5 Rx vs Placeb (%)
SOLVD	1992 NEJM	4228	Enalapril	Asymptomatic LV Dysfunctn	16.7	40	59.1	37.4	>2.5	1.2	NR	15.3	NR	NR	NR
Collaborative Study Group	1993 NEJM	409	Captopril	Renoprotection in IDDM+Proteinuri	75	450	35	36	>2.5	1.3	84	100	11 vs 21	NR	1 vs 0
REIN	1999 Lancet	186	Ramipril	Renoprotetion in non-diabetic CKD	5	20	49.5	32	CrCl ml/min20–70	1.9	54.5/BSA	0	50% reduct in ESRD	NR	Not Seen
ATLAS	1999 Circulation	3164	Lisinopril	HD vs LD ACEI in HF, EF <35%	33.2/4.5	80	63.6	46	>2.5	2176 hadS cr <1.5	NR	19	Not Different	10 vs 7	0.4 vs 0.1
RALES	1999 NEJM	1663	Spironolactone	Aldo blockade on MM in HF, EF<35	26	200	65	24	>2.5	NR	NR	NR	NYHA 3/494% ACEI	NCI	2 vs 1
CALM	2000 BMJ	199	Candesartan + Lisinopril	Renoprotecion in T2DM/HTN/Prot.	16/20	32/80	60	3	>1.7	1.0	100	100	Not Different	Not Seen	Not Seen
ELITE II	2000 Lancet	3152	Losaratan vs Captopril	MM, safety, Tol of AB in HF, EF<40	NR	100/450	71.4	18.5	>2.5	NR	NR	24	NR	NR	NR
MicroHOPE	2000 Lancet	3577	Ramipril	CV & Renal dx RR in H-risk DM	10	20	65.4	54	>2.3	1.1	NR	98	No difference	NR	NR
IRMA II	2001 NEJM	590	Irbesartan	Renoprotecion in T2DM/HTN/MA	150/300	300	58	24	>1.5	1.1 males0.9 females	109/BSA	100	No signi diff in Creat Cl	NR	NR
RENAAL	2001 NEJM	1513	Losartan	Renoprotecion in T2DM/HTN/Prot.	85.5	100	60	41	>3.0	1.9	NR	100	21.6 vs 26 (p = 0.006)	1.5 vs1.2	1.1 vs 0.5
IDNT	2001 NEJM	1715	Irbesartan	Renoprotecion in T2DM/HTN/Prot.	300	300	59	31	>3.0	1.7	NR	100	16.9 vs 23.7 (p = 0.008)	NR	1.9 vs 0.4
VALIANT	2003 NEJM	14703	Valsartan/ Captop/Both	MM in post-AMI HF; LVEF<40	V247/116/107	320/450	65	24.7	>2.5	1.1	NR	23	Exclud pts w Resp deterior	0.7 vs 0.7	NR
CHARMAlternative	2003 Lancet	2028	Candesartan	Candesaratan in HF Intol to ACEI	23	32	66.3	33.7	>3.0	NR	NR	30	5.5 vs 1.6 (p = 0.005)	6.1 vs 2.7	1.9 vs 0.3
CHARMPreserved	2003 Lancet	3023	Candesartan	Candesaratan in HF; Presvd EF>40	25	32	67.2	36.6	>3.0	NR	NR	28	6.0 vs 3.0(p = 0.007)	4.8 vs 2.4	1.5 vs 0.6
CHARMOverall	2003 Lancet	7601	Candesartan	Candesaratan in HF; OVERALL	24	32	66	37.7	>3.0	NR	NR	28	6.0 vs 4.0(p = 0.002)^§§	6.2 vs 3.0	2.0 vs 1.0
EPHESUS	2003 NEJM	6632	Eplerenone	Aldo block/MM inHF pAMI, EF<40	43	100	64	16	>2.5	1.1	79	32	86% on ACEI/ARB	Cr 0.06mg/dl h	5.5 vs 3.9
ALLHATPosthoc analysi	2005 Arch Int Me	33357	Lisinopril vs 2 other Rx	Treatment of High Risk HTN	60% on 40 mg	80	67	59	>2.0	1.0	78/BSA50–102	36	AmlodipineHigher GFR	ESRDNo diff	NR
Rossing et al	2005 Kidney Int	52	Irbesartan	Ultrahigh ARB inT2DM/HTN/MA	Up to 900	300	58	2	NR	NR	103/BSA	100	UH dose had −8ml/m vs −4 ml/m GFR	NR	NR

NR = not recorded.