Renzi quit as prime minister a year ago after losing a referendum on his planned constitutional reforms. He aims to return to power at the vote due by May, but the PD has split under his leadership and his prospects seem to be dwindling.
On Wednesday Giuliano Pisapia, a former mayor of Milan, announced that his small leftist party called The Progressive Camp (CP), which had been expected to join forces with the PD at the election, was disbanding.
Pisapia said it had proved 'impossible to continue talks with the PD', and complained in particular about Renzi's unwillingness to push through a contested law making it easier for the children of immigrants to obtain Italian citizenship.
Hours later, Foreign Minister Angelino Alfano, leader of the centrist Popular Alternative party (AP) which governs with the PD, said he would not be running at the election, throwing into doubt the future of the party he founded.
The CP and AP have less than 3 percent of the vote each, according to opinion polls, but the latest defections weaken the center-left in which a declining PD is now virtually without any allies.
'The left and the PD are crumbling away,' said Renato Brunetta, lower house leader of Silvio Berlusconi's Forza Italia (Go Italy!) party which is the lynchpin of a center-right alliance that is expected to win most seats at the election.
On Sunday, leftist parties which had already quit the PD joined forces under the leadership of Senate Speaker Piero Grasso to form Free and Equal, a new grouping already credited with around 6 percent of the vote and expected to grow further at the expense of the PD.
Renzi's PD critics say he has dragged the traditionally left-leaning party to the right and lament what they say is his autocratic, domineering leadership style.
The PD has been steadily losing support since it won over 40 percent of the vote at European elections in 2014. Surveys suggest it would now poll around 25 percent, some 3 points behind the anti-establishment 5-Star Movement.
The center-right bloc is made up of Forza Italia and the anti-immigrant Northern League, each with around 15 percent, and the right-wing Brothers of Italy, on around 5 percent.
While the center-right is seen winning most seats at the election, opinion polls suggest it will not win an absolute majority, making a hung parliament the most likely outcome.