Prostaglandin E1 for preventing the progression of diabetic kidney disease

Continuous albuminuria (protein in the urine) is the major characteristic of diabetic kidney disease (DKD), which is regarded primary cause of death and poor health in patients with diabetes mellitus, leading to end-stage-kidney disease. While blood pressure medication (such as angiotensin-converting enzyme inhibitors (ACEi), calcium channel blockers and angiotensin-receptor blockers (ARB)) has been used/recommended for reducing albuminuria and preventing the progression of DKD, the incidence of DKD is still increasing among developed and developing countries. Prostaglandin E1 (PGE1) is a vasodilator agent which is thought to contribute to releasing intraglomerular pressure, increasing kidney blood circulation and reducing albuminuria. This review identified six studies (271 participants) comparing PGE1 with or without ACEi/ARB versus ACEi/ARB, no treatment or Xueshuantong (a Chinese medicinal herb). The results suggest that PGE1 may have a positive effect on DKD by reducing urinary albumin excretion rate (UAER), microalbuminuria and proteinuria. No serious adverse events or allergic responses were reported. All studies were methodologically poor and there is no strong evidence for recommending PGE1 for preventing the progression of DKD as a routine therapeutic measure. More high-quality research is needed.

Authors' conclusions: 

PGE1 may have positive effects on DKD by reducing UAER, decreasing albuminuria and lessening proteinuria, with no obvious serious adverse events. However, limited by the poor methodological quality of the included studies and the small number of participants, there is currently insufficient evidence for determining if PGE1 could be used for preventing the progression of DKD. Large, properly randomised, placebo-controlled, double-blind studies are urgently needed.

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Background: 

Diabetic kidney disease (DKD) is one of the major chronic microvascular complications in diabetes mellitus, and may progress to end-stage kidney disease (ESKD). There are no definitely effective approaches for preventing, delaying or treating DKD. Small studies have shown that Prostaglandin E1 (PGE1) can improve renal blood circulation and decrease proteinuria and albuminuria.

Objectives: 

To assess the benefits and harms of PGE1 for preventing the progression of DKD.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Chinese Biomedicine Database (CBM) and reference lists of articles with no language restriction.

Selection criteria: 

All randomised controlled trials (RCTs) or quasi-RCTs comparing any PGE1 agent used for preventing the progression of DKD, regardless of dosage, mode of administration, addition of cointerventions or duration of treatment.

Data collection and analysis: 

Two authors independently assessed study quality and extracted data. For dichotomous outcomes (all-cause mortality, ESKD), results were expressed as relative risk (RR) with 95% confidence intervals (CI). Continuous outcomes (microalbuminuria, proteinuria, albuminuria, doubling of serum creatinine, serum creatinine) were expressed as mean difference (MD) with 95% CI.

Main results: 

Six studies (271 patients) were included. Five studies investigated PGE1 with or without fosinopril/losartan versus fosinopril/losartan or no treatment and one compared PGE1 versus Xueshuantong (a Chinese medicinal herb). There was a significant decrease in urinary albumin excretion rate (UAER) in patients treated with PGE1 (MD -48.28 µg/min, 95% CI -75.29 to -21.28), other outcomes also showed a significant decrease in the patients with PGE1 (albuminuria: MD -143.66 mg/24 h, 95% CI -221.48 to -65.84; proteinuria: MD -300 g/24 h, 95% CI -518.34 to -81.66). PGE1 had a positive effect on albuminuria (MD -660 mg/24 h, 95% CI -867.07 to -452.93) in clinical DKD (CDN, III stage of DN) compared with Xueshuantong. No data on incidence of ESKD, all-cause mortality or quality of life were available.

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