Stop chronic kidney disease progression: Time is approaching

Table 1 Standard of care therapeutic management

Drug class	On-target parameter	Off-target parameters	Ref.
Antihypertensive
RAS blockers	BP↓	UAE↓, GTP↓, K+↑, AT1-7↑, cytokines↓, Klotho↑	[53,54,56,69-82]
Aldosterone antagonists	BP↓	UAE↓, K+↑	[83-85]
K+ binders
Bisacodyl	K+↓	Diarrhea	[86]
Patiromer	K+↓		[87]
Na zirconium cyclosilicate	K+↓		[88]
Blood sugar control	Blood sugar↓	Progression↓	[93-95]
	HbA1c + 7	Postpones need of Dx
Hypocholestrolemic
Statins	Cholesterol↓, LDL↓	Cardiovascular events↓	[96]
Hypouricemic agents
Allpurinol	Uric acid↓	Renal events↓, CV events↓	[102,103]
Febuxostst	Uric acid↓	CKD progression↓	[104]
Sodium bicarbonate	HCO3-↑, PH ↑	Ptn catabolism↓, GFR decline↓	[105,106]
Phosphate binders
Calcium based	P↓	PTH↓, Vasc calc.↑	[117-120]
Sevelamer	P↓	PTH↓, stop vasc calc, Mortality↓, Uric acid↓, Cholesterol↓, LDL↓, inflammation↓ Cardiovascular events↓	[121-131]
Lanthanum carbonate	P↓	PTH↓, stop vasc calc,	[123-139]
Iron compounds	P↓	Iron↑	[140,141]
Nicotinamide	P↓	TG↓, LDL↓, HDL↑	[142-144]

RAS: Renin angiotensin system; BP: Blood pressure; UAE: Urine albumin excretion; GTP: Glomerular tuft pressure; K: Potassium; AT1-7: Angiotensin 1-7; Dx: Dialysis; LDL: low density lipoprotein; CV: Cardiovascular; CKD: Chronic kidney disease; HCO₃^-: Bicarbonate; Ptn: Protein; GFR: Glomerular filtration rate; P: Phosphorus; PTH: Parathormone; Vasc calc: Vascular calcification; TG: Triglycerides; HDL: High density lipoproteins.

Table 2 Novel therapeutic interventions

Therapeutic modality	Mechanism of action	Primary end points	Ref.
Chemokine ligand and receptor antagonists
CCR1 antagonists	Block CCR1 receptors on leucocyte surface	Leuc. Inf.↓, IF↓, TI↓, and improved KFTs	[146]
Emapticap pegol	Binds and neutralizes MCP-1	UAE↓, glycemic control in phase IV D.N.	[5,152,153]
CCX140	Block CCR2	UAE↓, glycemic control in phase IV D.N.	[6,154]
Pentoxifylline	Anti-inflammatory	UAE↓, eGFR loss↓	[156,157]
VDRA
Paricalcitol	Improves G.M. sieving, antifibrotic	UAE↓, eGFR loss↓	[160-162]
IAP
Mediterranean diet	Restores intestinal microbiota, IAP↑	eGFR loss↓	[184]
Bound phosphorus	IAP↑		[186]
Vitamin K	IAP↑		[188]
S.O.D. mimetic
Tempol	Oxidative stress↓	UAE↓, GS↓, TID↓	[189]
SRA
Sarpogrelate	Antiplatelet	UAE↓	[192]
V2RA
Tolvaptan	V2 receptor blocker	No. of cysts↓, growth of cysts↓	[19]
IgG anti-SAP antibodies	Binds SAP within amyloid tissue	Clearance of tissue amyloid deposits	[20]
RG-012	Inhibitor of miR-21	GS↓, IF↓, TI↓, Infl.↓	[22]

Leuc. Inf.: Leucocyte infiltration; IF: Interstitial fibrosis; TI: Tubular injury; KFTs: Kidney function tests; UAE: Urine albumin excretion; D.N.: Diabetic nephropathy; eGFR: Estimated glomerular filtration rate; VDRA: Vitamin D receptor agonists; G.M.: Glomerular membrane; IAP: Intestinal alkaline phosphatase; S.O.D.: Superoxide dismutase; GS: Glomerulosclerosis; TID: Tubulointerstitial disease; SRA: Serotonin receptor antagonist; V2RA: Vasopressin receptor antagonist; SAP: Serum amyloid protein; miR: Micro RNA; infl.: Inflamation.