Table 2. Studies of the microcirculation in animal models of CKD: heart.

First author	Year	Species (strain)	CKD model; CKD duration treatment	Main findings	Rarefaction [%] Compared with controls (method)	Ref.
Amann	1992	Rat (Sprague–Dawley)	5/6 NX; CKD for 14 months	HTN, left ventricular hypertrophy and MV rarefaction	25% (stereological evaluation)	[26]
Törnig	1996	Rat (Sprague–Dawley)	5/6 NX; CKD for 8 weeks + antihypertensive treatment	No HTN; reduction in MV density was completely prevented by Moxonidine and in part by Ramipril	22% (stereological evaluation)	[27]
Amann	1997	Rat (Sprague–Dawley) heart, M. psoas	5/6 NX; CKD for 8 weeks	HTN; myocyte cross-sectional area and interstitial tissue increased, MV density reduced in the heart but unchanged in M. psoas	23% in heart, none in M. psoas (stereological evaluation)	[24]
Amann	2000	Rat (Sprague–Dawley)	5/6 NX; CKD for 8 weeks ± Epo or Epo + antihypertensives (hydralazine+furosemide)	HTN; capillary rarefaction unchanged with Epo or Epo +antihypertensive treatment	25% (stereological evaluation)	[34]
Amann	2000	Rat (Sprague–Dawley)	5/6 NX; CKD for 15 weeks ± endothelin receptor antagonist or ACEi	HTN; MV density normalized with endothelin receptor antagonist, but not with ACEi	17% (stereological evaluation)	[35]
Amann	2000	Rat (Sprague–Dawley)	5/6 NX; CKD for 8 weeks ± ACEi or bradykinin receptor antagonist or both	No HTN; ACEi, but not bradykinin receptor antagonist abrogated MV rarefaction	29% (stereological evaluation)	[36]
Amann	2002	Rat (Sprague–Dawley)	5/6 NX; CKD for12 weeks ± α-Tocopherol (Vitamin E)	HTN; α-Tocopherol significantly attenuated MV rarefaction and interstitial fibrosis	24% (stereological evaluation)	[37]
Ogata	2003	Rat (Sprague–Dawley)	5/6 NX; CKD for 8 weeks ± PTX or calcimimetic	HTN; treatment significantly attenuated MV rarefaction and interstitial fibrosis	28% (stereological evaluation)	[39]
Gross	2005	Spontaneously hypertensive stroke-prone rat (Wistar–Kyoto)	½ NX; CKD for 12 weeks ± ovariectomy	HTN; significant improvement in MV density in ovariectomized rats treated with estrogens	n.a. (no controls without CKD)	[152]
Koleganova	2009	Rat (Sprague–Dawley)	5/6 NX; CKD for 12 weeks (or 4 weeks) ± calcimimetic	HTN; treatment with a calcimimetic attenuated rarefaction and interstitial fibrosis	Approx. 28% (15% after 4 weeks) (stereological evaluation)	[38]
Koleganova	2009	Rat (Sprague–Dawley)	5/6 NX; CKD for 12 weeks ± calcitriol	HTN; treatment with calcitriol ameliorated rarefaction and fibrosis	Approx. 25% (stereological evaluation)	[40]
Tyralla	2011	Rat (Sprague–Dawley)	5/6 NX; CKD for 8 weeks + 4 weeks antihypertensive treatment	HTN; treatment with ACEi, (but not with furosemide/hydralazine) improved myocardial fibrosis but not rarefaction	10%; unchanged by antihypertensive treatment (stereological evaluation)	[41]
Amann	2011	Rat (Sprague–Dawley)	(1) 5/6 NX; CKD for 8 weeks(2) 5/6 NX; CKD for 10 days ± renal denervation	No HTN; MV rarefaction prevented by renal denervation (after 10 days)	(1)18%;(2) 24% (stereological evaluation)	[33]
DiMarco	2011	Rat (Sprague–Dawley)	5/6 NX; CKD for 14 days ± calcineurin inhibitor, hydralazine	HTN; treatment with calcineurin inhibitors, but not hydralazine, normalized MV density	∼20% (lectin staining)	[42]
Gut	2013	Rat (Sprague–Dawley)	5/6 NX CKD for 16 weeks ± Epo + enalapril	HTN; treatment normalized MV density, ameliorated myocardial fibrosis in 5/6 NX rats	−15% in 5/6 NX (methylene blue/basic fuchsin staining)	[47]
Ali	2014	Rat (Wistar)	Adenine feeding (0.75%), 4 weeks ± gum acacia	HTN, myocardial hypertrophy, MV rarefaction ameliorated by treatment	Significantly decreased (with adenine; HE and PAS staining)	[50]
Di Marco	2015	Rat (Spague–Dawley)	5/6 NX ± sFlt-1 or VEGF121 infusion for 14 days (starting after NX)	HTN, MV density −15% in 5/6 NX treated with sFlt-1 and unchanged compared with sham-op. if treated with VEGF121	(lectin staining)	[48]
Golle	2017	Rat (Sprague–Dawley)	5/6 NX CKD for 14 days, ± bone marrow-derived cells or their conditioned medium	MV density significantly decreased, restored by treatment	−20% (lectin staining)	[44]
Prommer and Maurer	2018	Mouse (BALB/c) heart, M. cremaster	5/6 NX; adenine feeding (0.2%) CKD for 4 months (5/6 NX) or for 4 weeks (adenine)	No HTN; loss of coherent MV networks, large avascular areas, diminished blood flow velocity, vascular tone, oxygen uptake. Rarefaction in the cremaster muscle paralleled rarefaction in the myocardium. Decrease in mRNA levels of HIF-1α, Angpt-2, TIE-1 and TIE-2, Flkt-1 and MMP-9 in the heart	Progressive rarefaction with increasing severity of CKD (serum urea levels). Mean: 34% (5/6 NX); 43% (adenine)	[18]
Uchida	2020	Rat (Sprague−Dawley)	5/6 NX CKD for 6 weeks + N-nitro-l-arginine (nitric oxide synthase inhibitor), ± enarodustat (prolyl-hydroxylase inhibitor,)	HTN; enarodustat restored capillary density in heart and kidneys, ameliorated myocardial fibrosis without change in HTN	Significantly decreased (mouse anti-aminopeptidase P monoclonal antibody)	[151]